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FAB > Embryology > Flashcards

Embryology Flashcards

1
Q

What are the prerequisites for development ie to increase in size and complexity

A

Capacity to increase cell number

Capacity for differentiation

Capacity to organise in long range structures

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2
Q

What is menstrual age

A

From the first day of last menstrual period

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3
Q

What is conceptual/ fertilisation age (used most in lectures l)

A

Timing from first day of fertilisation

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4
Q

When are the foetal and embryonic stages?

A

Embryonic: first 2 months
Foetal: last 7 months

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5
Q

What are the Carnegie stages

A

A standardised system of 23 stages of development based upon anatomical features in the embryonic phase

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6
Q

What happens on day 0

A

Fertilisation

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7
Q

When is implantation

A

Day 7

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8
Q

When does gastrulation occur

A

Day 14

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9
Q

When is the beginning of neurogenesis

A

Day 16

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10
Q

When is the first functioning organ formed

A

Day 22 when the heart begins to beat

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11
Q

When does neural tube close occur

A

Day 27

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12
Q

When is quickening? What does this mean?

A

Day 112/ Week 16

Mother begins to feel movements of the foetus

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13
Q

When does the foetus become viable

A

Day 161/ week 23

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14
Q

Over which weeks does gastrulation and neurogenesis occur

A

3-8

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15
Q

Where does fertilisation occur and what does it result in

A

In the Fallopian tube forming a zygote

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16
Q

What happens day 3 (how many cells)

A

8 cell stage: embryo activates the genome (embryonic genome activation (EGA))

On day 4 compaction occurs and intercellular signalling begins

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17
Q

What does the first lineage decision establish

A

The trophoblast and inner cell mass

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18
Q

What does the second lineage decision make

A

Pluripotent epiblast and extraembryonic hypoblast

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19
Q

What does the hypoblast give rise to

A

The yolk sac

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20
Q

What happens days 6-7

A

Embryo hatches from zona pellucida and is now ready for implantation

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21
Q

Give the 3 populations in the late blastocyst

A

Epiblast
Hypoblast
Trophoblast

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22
Q

What is implantation

What kind of implantation do humans undergo

A

Attachment of late blastocyst to the uterus

Interstitial implantation with the blastocyst penetrating the endometrial lining

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23
Q

What does the epiblast specify and form

A

Amnion, forming the amniotic cavity and gives rise to the embryonic disc

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24
Q

What happens to hypoblasts

A

Expand and form the primary and secondary yolk sac

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25
Q

What does trophoblast diversify into

A

Cytotrophoblast and syncytiotrophoblast

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26
Q

What are lacunae

A

Cavities in the syncytiotrophoblast, which play an important role in embryo nutrition prior to development of the placenta

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27
Q

3 germ layers?

A

Ectoderm - outermost layer
Mesoderm- middle layer
Endoderm- innermost layer

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28
Q

What is induction

A

One cell type (the inducer) induces the fate of another cell type (responder)

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29
Q

What coordinates gastrulation

A

Hypoblast

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30
Q

What does the ectoderm form

A

Skin and nervous system

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31
Q

What does the mesoderm form

A

Muscles, connective tissue, bones and circulatory system

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32
Q

What does the endoderm form

A

Digestive and respiratory system + other internal organs

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33
Q

What is the gut formed from

A

The inner of the 3 concentric tubes generated when the 3D embryo is formed (ie the endoderm)

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34
Q

What does the gut tube initially consist of

A

Blind ending tubes at the cranial and caudal ends and a central portion, the midgut that still connects to the yolk sac

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35
Q

Where does the foregut terminate

A

The buccopharyngeal membrane (which goes on to form the mouth and nose)

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36
Q

Where does the hind gut end

A

The cloacal membrane

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37
Q

What does the cloacal membrane go on to form

A

urogential and rectum

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38
Q

What forms the thoracic part of the foregut

A

The stomach

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39
Q

Which side of the stomach grows faster

A

The dorsal wall grows faster than the ventral wall resulting in the ventral lesser curvature and dorsal greater curvature

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40
Q

What happens after the curvature of the stomach is formed

A

It undergoes a 90 degree rotation about the cranio-caudal axis so that the greater curvature lies on the left and the two branches of the vagus nerve that were left and right now lie anterior and posterior respectively

There is an additional tilting caudally which orientates the great curve so that is inferior

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41
Q

What is formed as a result of stomach rotation

A

The lesser sac

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42
Q

Discuss pyloric stenosis

A

3/1000 affected
Male babies 2-8 weeks most at risk
Symptoms: forced projectile vomiting leading to severe dehydration
Requires surgery

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43
Q

Where does the hepatic diverticulum sprout from

What happens next

A

The duodenum into the ventral mesentery

Interacts with the surrounding septum transversum mesenchyme

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44
Q

What does the liver bud require

A

An indicative signal from the heart mesoderm

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45
Q

How do we know that heart mesoderm is essential for inducing liver development

A

If early pre liver endoderm is explanted with Pre liver mesoderm alone, no liver differentiates but with both pre-heart and - liver mesoderm, well formed hepatic cords develop

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46
Q

What are the signals from the heart mesoderm to the developing liver

A

Growth factors eg FGF1 and FGF2

Also promote liver specific gene transcription by blocking inhibitory factors present in the endoderm

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47
Q

What happens after hepatic specification

A

Endothelial cells intercede between hepatic endoderm cells and the septum transversum mesenchyme. They promote the morphogenesis phase of organogenesis

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48
Q

What happens in the morphogenesis phase of hepatic development

A

Hepatogenic cells multiply and migrate into the septum transversum mesenchyme to develop the liver bud and ducts

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49
Q

What happens to the lateral plate mesoderm surrounding the newly formed liver bud

A

Becomes the supporting stroma

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50
Q

What is the cystic diverticulum

A

It sprouts from the base of the hepatic bud and forms the gall bladder and cystic duct

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51
Q

Give an overview of the development of the pancreas

A

Forms from 2 buds: dorsal (forms first) and ventral (grows more slowly)
Buds are induced by endoderm, adjacent mesoderm and ectoderm (eg notochord) allowing them to emerge and develop
Then first pancreatic-specific genes (eg Pdx1) are expressed
Exocrine and endocrine tissue is formed
2 buds eventually fuse when the smaller ventral bud migrates round and meets the dorsal bud

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52
Q

What does exocrine pancreatic tissue produce

A

Amylase and α- fetoprotein

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53
Q

What does endocrine pancreatic tissue produce

A

Insulin
Glucagon
Somatostatin

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54
Q

What regulates the ratio of exo to endocrine cells

A

Follistatin which is secrete by the pancreatic mesenchyme

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55
Q

What forms the uncinate process

A

The pancreatic ventral bud

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56
Q

What is an annular pancreas

Give a complication and it’s incidence

A

If the ventral bud is duplicated migrating lobes can encircle the duodenum
Affects 1/7000 people
May result in narrowing or constriction of duodenum

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57
Q

Why does herniation occur in gut development

A

The extensive growth of the midgut, especially the ileum, leads to it growing faster than the abdomen and the primary intestinal loop formed is forced out into the umbilical cord, carrying with it the superior mesenteric artery

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58
Q

What happens to the developing herniated loop

A

Rotates 90 degrees anti-clockwise (programmed by left right organisation)
The continued lengthening of the duodenum and the jejunum gives rise to a series of folds and the midgut is retracted, rotating a further 90
Finally the caecum moves inferiorly, completing the 270 degree rotation

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59
Q

What is omphalocele

A

When the umbilical ring doesn’t close and the loop of midgut remains outside the abdominal wall in a peritoneal sac

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60
Q

What is Mickel’s Diverticulum

A

Finger like pouch on antemesenteric border of ileum

It is a failure of the Vitelline duct to regress completely

It may rotate and obstruct

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61
Q

What can abnormal gut rotation lead to

What is needed to diagnose

A

Freely suspended coils of intestine prone to torsion or volvulus

Barium meal/ enema

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62
Q

Where does the kidney develop from

What are its 3 phases of development

A

The intermediate mesoderm

Pronephros -> mesonephros -> metanephros

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63
Q

When does the urogential ridge begin to form and in what direction

A

In week 4 in a rostral caudal direction

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64
Q

Discuss pronephros development

A

Begins to develop at day 24 between somites 3-5 with the duct forming between somites 5-7

It is a rudimentary structure in higher vertebrates but is essential for embryonic survival of fish and amphibians

It degenerates v rapidly and is never functional in humans

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65
Q

Discuss the development of the mesonephros

A

Differentiates from ~28 days and begins to regress at the cranial end at 5 weeks

Never has more than 30 nephrotomes
It produces dilute urine

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66
Q

Briefly describe metanephros development

A

Ureteric bud grows out of the mesonephric duct at ~5 weeks and induces formation of the metanephric kidney

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67
Q

How do the tubules in the mesonephros form

A

In cranio-caudal succession

Earlier tubules degenerate as later ones form so usually ~30 tubules at any time

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68
Q

Is the mesonephros functional

A

Yes it is functional in the embryo, producing a dilute urine important in maintaining the composition of amniotic fluid

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69
Q

How can you show experimentally what induces Kidney development

A

By artificially placing a barrier between the ureteric bud and surrounding cells to stop movement of secreted proteins stops kidney development

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70
Q

Define induction

A

Alteration of the fate of a cell or tissue by interaction with a second

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71
Q

What are the phases of initiation

Give a description of each in the context of kidney development

A

Initiation: signals from metanephrogenic mesenchyme induce growth of ureteric bud

Commitment to development: response to inducing signals - proliferation and differentiation of bud and mesenchyme

Morphogenesis: in response to signals from mesenchyme bud commences branching morphogenesis, mesenchyme responds by becoming epithelial in nature and forming nephrons

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72
Q

Give the 2 key consequences of induction in kidney development

A

Ureteric branching morphogenesis

Epithelial morphogenesis

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73
Q

Describe the epithelial morphogenesis in kidney development

A

The mesenchyme to epithelial transition occurs in response to Wnt expression
Formation of S shaped bodies
Thins on one side to form glomerulus
Fuses with UB tip
Extends to form proximal and distal tubules

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74
Q

What causes outgrowth of ureteric bud towards metanephrogenic mesenchyme

A

Production of glial derived neurotrophic factor (GDNF) by MM which binds to the Ret receptor expressed on ureteric buds

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75
Q

What does the ureteric bud induce the mesenchyme to do

A

Condense around the tips of the branching ureteric epithelium and time undergo MET to form renal vesicles

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76
Q

What is MET

A

Mesenchyme to epithelial transition

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77
Q

What triggers MET

What does this do

A

Wnt signalling via secretion of Wnt9b from the ureteric tip

Upregulates (Fgf8) and Wnt4 production by the MM

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78
Q

What does Fgf4 do

A

Stimulates proliferation of mesenchyme

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79
Q

What does Wnt4 do

A

Regulates formation and differentiation of the comma and S shaped bodies to form renal vesicles

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80
Q

What follows induction at the ampulla in kidney development

A

The bud branches and a nephron forms

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81
Q

What is dichotomous branching

What does it give rise to from the ureteric bud

A

Branching that results in the regular form of the kidney

It gives rise to the collecting ducts while the surrounding cells wil form the nephron and convoluted tubules

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82
Q

When does the mean glomerular number level off

Is this the end of kidney development

A

36 weeks

No, nephrogenesis and functional maturation continues after birth

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83
Q

What is the differential lineage if nephron cells

A

There are different lineages;

Collecting duct is from the ureteric bud
Convoluted tubules and glomerulus from the metanephric blastema

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84
Q

Where do renal blood vessels come from

A

Smaller vessels are derived by vasculogenesis within the kidney

Larger vessels were developed by angiogenesis and invaded the kidney from the renal arteries

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85
Q

How common is developmental abnormality in the urinary tract

Do all cause clinical problems

A

10% of all new norms

No but if the ureteric bud does not reach/ signal properly to mesoderm the kidneys don’t form (agenesis)

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86
Q

What are polycystic / dysplastic kidneys

A

Kidneys whose tubules failed to form correctly and may continue to proliferate

Bifurcated ureters may also occur due to defects in induction

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87
Q

What is the mean globular number at 15 and 40 weeks and then in the adult

How does this relate to disease

A

15:15000
40: 740000
Adult: 617000 (declines with age)

Related to risk of hypertension
Genetically induced reduction in nephron number in mice is associated with high blood pressure
Number of nephrons is strongly related to birth weight

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88
Q

How are nephron number and birth weight related

A

Babies with birthweight below 10th percentile have 30% fewer nephrons

This is the developmental programming hypothesis

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89
Q

What happens after the mesonephric duct and ureteric bud enter the urogential sinus

A

In the Male the mesonephric duct migrates inferiorly to enter urethra Asia has deferens But regresses in females

Ureteric bud grows and elongates to become ureter and the portion closest to the urogential sinus splays out to generate posterior bladder wall

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90
Q

What is the trigone

A

The posterior wall of the bladder

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91
Q

Discuss the urachus in the foetus

A

It constitutes the connection between the developing bladder and the allantois, so runs from the bladder to the umbilicus and umbilical cord

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92
Q

What happens to the urachus

A

Normally fibroses after delivery forming the median vesical ligament

If this fails a urachal fistula May develop, resulting in urine leaking from the umbilicus

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93
Q

Where do the gonads develop

A

On the medial side of the mesonephric ridge (the urogential ridge)

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94
Q

When does te genital ridge firm

When do gonads differentiate

A

5-6 weeks
On medial side of mesonephros

After 7-8 weeks of gestation

Associated with dual ductal system

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95
Q

Why is urogential development associated with a dual Ductal system

A 
Wolffian (mesonephric) ducts firm first
Then Mullerian (paramesonephric) ducts Form laterally

Ducts form by invagination of the coelomic epithelium

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96
Q

Do primordial germ cells begin at genital ridges

A

No they migrate by amoeboid movement from the hindgut along the dorsal mesentery around weeks 4-6

They are guided by chemitaxis

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97
Q

What does sex determination depend upon

A

Presence or absence of Y chromosome

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98
Q

What allows Y and X to pair at meiosis

A

Y retains homology with X at telomeres as they arose from a common ancestor

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99
Q

What are the gonadal and somatic sex structures in males

A

Gonadal: testis
Somatic: penis, scrotum, prostate, vasa

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100
Q

What are the gonadal and somatic sex structures in females

A

Gonad: ovary

Somatic: clitoris, vagina, uterus, oviducts

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101
Q

Where is SRY located

What does this position allow

A

Near the end of the short arm of Y

Allows SRY to be exchanged in crossover events between X-Y or completely lost
Exchange can lead to sex reversal

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102
Q

What are the 3 phases of limb development

A

Limb bud outgrowth and patterning

Morphogenesis

Growth

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103
Q

What do limb buds consist of

A

A core of loose Mesenchyme and and an ectodermal layer

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104
Q

What is the AER

A

The apical ectodermal ridge
A thickening of ectoderm the tip of the developing limb

Plays a critical role in outgrowth

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105
Q

What does removal of the AER do

A

Leads to a truncated limb

The earlier the AER is removed the less developed the limb is

This suggests AER produces a signal promoting proximal distal development of the limb

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106
Q

What happens if a chick’s AER is grafted onto the lower limb bud in place of leg AER

Give another example to prove the same effect

A

Bud will still produce a leg

Mouse AER can substitute for chick AER

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107
Q

Which is the important protein secreted by the AER

How do we know this

A

FGF8

If AER is replaced by bead of FGF8 an almost normal limb still develops

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108
Q

What is FGF4

A

Works similarly to FGF8 and is expressed in posterior AER

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109
Q

Why does older mesenchyme give more distal structures?

A

The structures formed depend on the length of time exposed to FGF

Cells close to the FGF source remain undifferentiated and don’t differentiate until out of reach of FGF

Cells exiting first form proximal structures, cells exposed for longest form distal structures

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110
Q

What is SHFM

A

Split Hand Foot Malformation

Rare limb condition linked to AER failure

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111
Q

Discuss thalidomide’s effect on development

A

Prevents proliferation of cells in progress zone so cells are exposed to FGF for longer and develop as more distal structures (phocomelia - a loss of proximal limb structures)

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112
Q

Where is the AER located

A

Boundary between dorsal and palmar on limb bud

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113
Q

How is dorsal palmar patterning coordinated

A

Ectoderm produces signals to confer dorsal/ palmar information

Wnt7a is produced by dorsal part only. This diffuses into the mesoderm where it induces expression of genes that coordinate dorsal fates

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114
Q

Describe 2 experiments showing the importance of Wnt7a and the ectoderm in dorsal palmar development

A

If ectoderm is removed and replaced back to front, hand develops back to front

If Wnt7a is removed in mouse embryos, double ventral limbs develop

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115
Q

What happens if you graft the posterior zone of one limb into the anterior of another limb

A

It leads to a limb with mirror image duplication of digits

This is affected by position of graft, which suggests the cells produce a diffusible signal and the type of digit formed depends on the concentration of signal that the cell is exposed to

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116
Q

What is the morphogen concept

A

the cells produce a diffusible signal and the type of digit formed depends on the concentration of signal that the cell is exposed to

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117
Q

Which signal is important in digit formation and patterning (ZPA)

Prove it

A

Sonic Hedgehog

SHH transplantation shows that number and identity of digits formed depends on concentration of SHH

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118
Q

What causes polydactyly

A

Mutated SHH

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119
Q

What regulates Hox genes

A

SHH regulates their expression

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120
Q

Discuss Hox genes

Which are important for limb development

A

Found in 4 clusters in mammals (a-d)

Hox d

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121
Q

What results in syndactyly

What is it and how is it treated

A

Mutated Hox d13

Results in fusion of digits
Zig zag incisions to give skin flaps to cover cut region

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122
Q

What do the initial phases of skeletogenesis involve in the limbs

A

Formation of cartilage condensations regulated by GDF5

Bone Initiates in the mesenchyme, GDF5 increases condensation

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123
Q

What happens if you abnormally increase GDF5

A

Abnormal bone growth / thickening

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124
Q

What is CGT and CHTT

A

Chondrodysplasias Grebe type
And Hunter Thompson type

Caused by mutations in GDF5

Pronounced shortening of skeletal elements

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125
Q

How is cartilage converted to bone

A

Ossification

Growth hormone, thyroid hormones and IGF1 all influence bone growth by acting on germinal zone stem cells

FGF3 inhibits growth and promotes differentiation

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126
Q

Where is the FGF3 receptor present

A

Chondrocytes

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127
Q

What causes dwarfism

A

Achondroplasia is associated with an activating mutation in FGF3R

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128
Q

What happens if FGF is exposed to the flank

A

A new limb grows with AER and ZPA

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129
Q

What ensures limbs grow in the right place

A

Tbx5 expression

Defects in Tbx5 are associated with Holt Oran syndrome

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130
Q

Which limbs position upper and lower limbs

A 
Tbx5 = upper 
Tbx4 = lower
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131
Q

When does the zygote undergo cleavage

What is this

A

Days 1-5

Cell division in the absence of cellular growth. There is no increase in total cell mass

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132
Q

Which part of the fertilised egg is cleavage dependent on

A

The large cytosolic compartment

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133
Q

What happens at day 3

A

This is the 8 cell stage

Here the human embryo activates the genome

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134
Q

What is EGA

A

Embryonic genome activity

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135
Q

When does compaction occur

How many cells are there here

A

Day 4

8

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136
Q

When does cavitation occur

What also happens here

A

Day 4-5
The morula becomes the early blastocyst

The first lineage decision occurs here

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137
Q

What does the first lineage decision establish

A

Trophoblast and Inner Cell Mass (ICM)

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138
Q

What is the trophoblast and what does it give rise to

What does the ICM form

A

An extra embryonic lineage

Gives rise to the placenta

ICM forms the embryo

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139
Q

What happens days 6-7

A

ICM undergoes 2nd lineage decision

The embryo hatched from the zona pellucida

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140
Q

at the second lineage decision, what does the ICM differentiate into

A

The pluripotent epiblast and the extraembryonic hypoblast

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141
Q

What does the hypoblast give rise to

What about the epiblast

A

The yolk sac

The epiblast is the founding population of the entire foetus

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142
Q

When is the embryo ready for implantation

A

Days 6-7 when the embryo hatched from the zona pellucida

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143
Q

The human late blastocyst has established which 3 founding populations

A

Epiblast
Hypoblast
Trophoblast

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144
Q

What is embryo implantation

A

Attachment of the late blastocyst to the uterus

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145
Q

What kind of implantation do human embryos undergo

A

Interstitial implantation where the blastocyst penetrates the endometrial lining

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146
Q

Where does the amnion come from

What related structures are also formed from this

A

The epiblast specifies the amnion, forms the amniotic cavity and gives rise to a flat embryonic disc

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147
Q

What is Heuser’s Membrane

A

The secondary yolk sac, derived originally from the hypoblast

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148
Q

What does the trophoblast mediate

A

Invasion intro maternal tissue

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149
Q

What does the trophoblast diversify into

A

Cytotrophoblast (proliferative compartment)

Syncytiotrophoblast (multinucleate cells)

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150
Q

What forms lacunae

What is the role of these embryonic lacunae

A

Cavity formation in the syncytiotrophoblast

Embryo nutrition prior to development of the placenta

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151
Q

What did Wolpert say of Gastrulation

A

“It is not birth, marriage, or death, but gastrulation which is truly the most important time in your life”

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152
Q

What are the 3 germ layers and when are they established

A

Ectoderm
Mesoderm
Endoderm

Established during gastrulation

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153
Q

Gastrulation is simply the formation of the 3 germ layers. True or false

A

False

Gastrulation also ensures correct positioning of the germ layers as a result of cell differentiation and relocation

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154
Q

When does Gastrulation occur

A

~day 14

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155
Q

What coordinates Gastrulation

A

Hypoblast

156
Q

What happens to the epiblast cells of the embryonic disc in Gastrulation

A

They delaminate and migrate through the primitive streak in between epiblast and hypoblast

157
Q

What does ectoderm give rise to

A

Epidermis and nervous system

158
Q

What does the mesoderm give rise to

A

Muscle
Connective tissue
Bones
Circulatory system

159
Q

What does the endoderm produce

A

Digestive system
Respiratory system
Internal organs

160
Q

How many cells are in a morula

A

~128

161
Q

What are the 2 sections of the blsatocyst

A

The inner cell mass and trophoectoderm

162
Q

What are the fetal membranes

A

The amnion
Yolk sac
Allantois
Chorion

163
Q

What is the amnion

A

A fluid filled sac surrounding the embryo, providing a protective aqueous environment for the developing foetus

164
Q

What is the yolk sac

A

A highly vascular extra embryonic membrane

It provides the nutrient supply prior to the formation of the placenta

165
Q

Where do the first blood cells originate

A

The yolk sac

166
Q

What is the allantois

A

An extension the yolk sac into the connecting stalk to act as a source of embryonic blood cells

167
Q

What is the chorion

A

The fetal component of the placenta

It is highly vascular for gas exchange, waste management, and nutrient transport during fetal growth

168
Q

Are humans diploblastic or triploblastic

A

Triploblastic - human embryos have 3 germ layers

169
Q

What is a diploblastic animal

A

Animals whose embryos have only 2 germ layers

Eg Hydra

170
Q

What 2 germ layers do diploblastic animal embryos have

A

Ectoderm and endoderm

171
Q

How is Gastrulation induced

A

Induced in the epiblast by the hypoblast through transmission of diffusible peptides

172
Q

How does the embryo specialise

A

Inside out

173
Q

When is the head tail axis of the embryo defined

A

Cell migration at the primitive streak

174
Q

What have all embryos acquired by the end of Gastrulation

A

A body axis with a head and tail end

An inside out specialisation with 3 basic layers

A left right axis

175
Q

What organises the main body axis

A

The node or primitive knot

176
Q

What happens if you graft Hesen’s node from a quail embryo to a chick embryo

A

The chick embryo will have 2 axes: the host axis and the induced axis from the transplanted node

177
Q

Discuss conjoined twins

A

Identical twins who develop with a single placenta from a single fertilised ovum
More common in females (3:1)
Mechanism responsible is probably a failure for twins to separate after Gastrulation (day 13)

178
Q

How common are conjoined twins

A

1 in 40,000 but only 1 in 200,000

179
Q

How is the embryonic endoderm formed

When does this occur

A

Hypoblast induces epiblast cells to undergo a an epithelial-mesenchymal transition.
These cells leave the primitive streak and invade the hypoblast, forming the definitive endoderm

Day 16

180
Q

How is the mesoderm formed

A

After the formation of the endoderm, epiblast cells migrate into the space between the endoderm and the epiblast.
The mesoderm forms 5 separate layers.

181
Q

How many layers does the mesoderm form?

What are they?

A

5

Cardiogenic mesoderm
Axial mesoderm (AKA notochord)
Paraxial mesoderm 
Intermediate mesoderm
Lateral plate mesoderm
182
Q

What happens once the endoderm and mesoderm are formed

A

Migration ceases and the epiblast becomes ectoderm

183
Q

How does the notochord form

A

Days 19-21: there is invagination from the primitive node and axial cell migration
The notochord grows anteriorly

184
Q

What does the formation of the notochord do

A

Determines longitudinal axis for the future differentiation of the vertebral body

Induces epiblast differentiation to become neural plate

185
Q

Which part of the mesoderm is primarily involved in neurulation

When does this occur

Which to germ layers are involved

A

Notochord

Day 19 onward

Communication between mesoderm and ectoderm

186
Q

Give evidence that the mesoderm induces neural tube formation in the ectoderm

A

Transplantation of a second notochord leads to a duplicate neural tube

Any ectoderm transplanted next to the notochord will be induced to form neural tissue

187
Q

When do the anterior neural folds close

A

The later part of the 4th week

188
Q

When does the posterior neuropore close

What becomes evident here

A

2 days after the anterior

An upper limb bud is evident

189
Q

Give 2 defects caused by a failure of the neural tube to close

What are each caused by

A

Anencephaly - failure of anterior neuropore closure

Spina bifida - failure of posterior neuropore closure

190
Q

What may cause defects in neural tube closure

How frequent are they

A

Folate deficiency
Valproate (drugs)
Cholesterol metabolism

1/300 - 1/5000

191
Q

What does the neural crest develop

A

Schwann cells
Neuroglial cells
SNS
PNS

192
Q

What does the neural tube form

A 
Brain
Neural pituitary 
Spinal cord 
Motor neurons
Retina
193
Q

What does the outer ectoderm form

A 
Epidermis
Hair
Nails
Teeth enamel 
Anterior pituitary
194
Q

When do epiblast cells undergo transition to epithelial mesenchyme

What signals this

A

16 days

Underlying hypoblast

195
Q

What layers does the lateral plate mesoderm divide into

A

Somatic

Visceral

196
Q

4 facts about somites

A

Derived from paraxial mesoderm
Transient structures
Formed in pairs that flank to midline
Formed sequentially from cranial to caudal

197
Q

When do somites begin to form

A

21 days

198
Q

What is the clock and wavefront model

A

Describes somitogenesis in vertebrates
Mainly controlled by retinoic acid and FGF (these are antagonistic)
Every 90mins a new pair of Somites form
Negative feedback loop

199
Q

What are the 3 types of somite

A

Myotome
Sclerotome
Dermatome

200
Q

What do the myotome somites form

A

Epaxial (dorsal) and hypaxial (ventral) muscles of trunk and limbs

201
Q

What does the sclerotome form

A

Axial skeleton, vertebrae and ribs

202
Q

How are the vertebrae formed from somites

A

1 vertebra formed from 2 half sclerotomes on each side of the notochord

203
Q

What disease spreads and shows a single dermatome

A

Zoster

Blistering in a single dermatome

204
Q

What dictates a somite’s fate?

A

It’s cranial caudal position

Eg ribs will form from thoracic somites

205
Q

Give experimental evidence that the fate of a somite depends on its position

A

If you transplant a somite from one region to another region it will grow structures appropriate to the original site

206
Q

Which class of gene family controls correct axial specification of somites

What do these genes do

A

Hox

Give each segment an address/ specification

207
Q

What happens if Hox expression is perturbed

Give an example/ evidence

A

Structures will form in the wrong place

Eg ribs can grow in lumbar and sacral vertebrae in Hox gene knockout mice

208
Q

What is aristapedia

A

Hox gene mutation leading to flies having legs in the place of their antennae

209
Q

What is the motif found in Hox genes

What does it do

A

The homeodomain

Activates or inhibits downstream genes concerning axis patterning, migration, cell death etc

210
Q

Give an example of how Hox genes determine number and types of vertebrae in different animals

A

Hoxc -6

In chicks this determines that 7 vertebrae will develop into ribs

In snakes Hoxc-6 is expanded dramatically towards the head and towards the rear so there are many more vertebrae which develop ribs and lose limbs

211
Q

How common are cervical ribs?

What might cause it

A

<1% live births

Spontaneous homoeotic mutation

212
Q

How many Hox genes are implicated in human heritable diseases

A

> 27

213
Q

Spinal nerve segmentation comes before somite organisation

True or false?

A

False

The segmental Organization of the spinal nerves is secondary to that of the somites

214
Q

What does coelom mean

A

Cavity in Greek

215
Q

What forms the thoracic cavity

A

Cranial folding

216
Q

Where is the cardiogenic region originally

When

How does it move

A

Near the forebrain

In the flat embryonic disc

Cephalic growth displaces the cardiogenic region and is folded underneath, coming to lie on the ventral surface of the chest

217
Q

How is the septum transversum first seen

Where does it move to during folding

A

As a thick bar of mesoderm between the cardiogenic region and the cranial margin of the embryonic disc

Lies between cardiac region and neck of yolk sac, separating thoracic and abdominal cavities

218
Q

What does the septum transversum form

A

Part of the diaphragm

219
Q

What innervates the diaphragm

Why is this not surprising

A

Cervical nerves (phrenic nerve: C3,4,5)

Septum transversum was originally adjacent to forebrain

220
Q

What does the ventral folding of the embryo produce

A

Intraembryonic coelom lined with mesoderm

221
Q

Intraembryonic coelom is lined with mesoderm. What does the mesoderm form?

A

The serous membranes (Parietal and visceral)

222
Q

Where are the somatic and splanchnic mesoderm

What are their other names

What is the space between them called

A

Somatic (parietal) mesoderm: outer layer, beneath the ectoderm

Splanchnic (visceral) mesoderm: overlying the endoderm

Coelom

223
Q

How does the dorsal mesentery form

A

Primitive gut tube hangs from the posterior body wall by a broad bar of mesentery
Below the septum transversum, the mesenteric bar thins out to form the more membranous dorsal mesentery That suspends the abdominal viscera in the coelomic cavity

224
Q

Name 2 visceral organs that develop in the body wall

What group are these a part of

Why is this

A

Kidney
Bladder

Retroperitoneal organs

These organs are separated from the coelom by a covering of serous membrane

225
Q

What separates the thoracic cavity

A

Pleuropericardial folds arise from the lateral body walls and grow medially towards each other separating developing lungs from the heart.

They meet and fuse forming the pericardial cavity and the pleural cavities (right and left)

226
Q

How common are congenital pericardial defects

What does this involve

A

1/14000
3x more common in men

Persistent pleuropericardial foramen due to arrested development of pleuropericardial folds

227
Q

What is the diaphragm formed from

A 
4 structures
Septum transversum
Pleuroperitoneal membranes 
Muscular components of lateral body walls
Dorsal mesentery of oesophagus
228
Q

How common is congenital diaphragmatic hernia

What is it

How is it diagnosed

A

1/2000 to 1/5000

Failure of diaphragm to fuse allowing developing developing abdominal viscera to bulge into pleural cavity. If large enough this may stunt the lungs.

Using ultrasound

229
Q

What is the usual cause of failure of diaphragm fusion

A

One of pleuroperitoneal membranes fails to meet septum transversum

230
Q

How does a congenital diaphragmatic hernia present

A

Severe pulmonary hypoplasia and pulmonary hypertension
Scaphoid abdomen
Severely affected babies will be symptomatic after birth. Most will develop symptoms within 24 hours

231
Q

What is a scaphoid abdomen

A

Boat shaped

Anterior abdominal wall is sunken and presents a concave contour

232
Q

What induces lung development?

Prove it

A

Mesoderm

If cultured alone, a lung bud shows no further differentiation

If a lung bud is cultured with stomach mesoderm, gastric glands are formed

If the lung bud is cultured with intestinal mesenchyme, villi form

If developed with bronchial mesoderm, bud branches

If developed with tracheal mesoderm collagen forms but there is no branching

233
Q

What is the respiratory diverticulum

A

When two tracheo oesophageal ridges start to separate the oesophagus from the lung bud

234
Q

What happens to the lung bud after the respiratory diverticulum is formed

What happens to the tracheo-oesophageal ridges

A

Lung bud bifurcates into the precursors to the 2 bronchi and lungs

They fuse to divide the oesophagus from the trachea and the laryngo-tracheal endoderm becomes the lining of the trachea and the rest of the airway

235
Q

What is TEF and how common is it

A

Tracheoesophageal fistula
OR
oesophageal atresia

Failure to separate trachea and oesophagus
Causes severe choking in neonatal baby

1/5000

236
Q

Describe the signals that coordinate lung branching

A

FGF10 is secreted by mesoderm and guides bronchial branching

FGF10 induces new gene expression in the cells at the ends of the bronchial branches

SHH acts as negative feedback, inhibiting FGF10 expression locally. This stops outgrowth, promoting next round of branching.

237
Q

How many live births are affected by congenital cardiovascular abnormalities

A

1%

238
Q

What is the earliest functioning organ?

When does it begin to function?

A

The heart

Starts to beat at 22 days

239
Q

When can the heart first start to propel fluid

A

24 days

240
Q

What are the 4 structural shapes the heart goes through in development

A

Cardiac crescent
Linear heart tube
Looping heart
Remodelling heart

241
Q

How are cardiac progenitors first recognisable

A

As a crescent shaped epithelium

242
Q

How does the linear heart tube form

A

Heart progenitors move ventrally to form the linear heart tube, compromising an endothelial lining (endocardium) enveloped by a myocardial epithelium

243
Q

How does blood flow through the linear heart tube

A

In flow caudal, outflow cranial

244
Q

How does the linear heart tube form the looping heart

A

The tubular heart adopts a spiral shape. The inflow portion, including the common atrium, is forced dorsally and cranially so ends up above the developing ventricles

245
Q

How is the heart remodelled after the looping heart stage

A

Heart divided into chambers by septation

This leaves distinct left and right ventricles and atria

246
Q

How many sides of the heart tube has a thick layer of mesoderm

What does this become

A

3 sides

Myocardium

247
Q

What is cardiac jelly

A

A gelatinous acellular matrix, secreted by the myocardium, separating the myocardium and endocardium

248
Q

What are the primitive chambers of the heart

A 
A series of bulges which form:
Sinus venosus
Primitive atrium
Ventricle
Bulbus cordis
Truncus arteriosus
249
Q

How does the linear heart pump

What prevents back flow

Where is blood expelled

A

Contractions begin at the sinus venosus (which acts as the pacemaker) and a wave of muscle contraction is propagated up the tubular heart

Cardiac jelly and constrictions

From the truncus arteriosus

250
Q

When is the patterning of the heart initiated

How do we know this

A

During Gastrulation

In the linear heart the primitive atrium and ventricle have different cardiac myosin

251
Q

What happens on day 23

A

The heart begins to elongate and fold and loop

252
Q

What does looping of the heart do

A

Displaces bulbus Cordis inferiorly, ventrally and the right

Displaces primitive ventricle to the left

Displaces the primitive atrium posteriorly and superiorly

253
Q

When is heart looping complete

A

By day 28

254
Q

What forms the outflow regions of the ventricles

What about the actual ventricles

A

Superior end of Bulbus cordis

Inferior end of bulbus cordis forms most of right ventricle
Primitive ventricle forms most of left ventricle

255
Q

Where does the base to apex heart axis point

What is it called when this is reversed

What is the name when all organs are swapped on the left-right axis

A

Left

Dextrocardia

Situs inversus

256
Q

When does left right patterning begin

Elaborate

A

Gastrulation

The nodal gene is only transcribes in cells on the left side of the primitive streak

257
Q

Where does our understanding of left right asymmetry come from

A

Studies of 2 mouse mutants

258
Q

What is the inv mutation

What is nodal

A

In version of turning

Results in 100% reversal of looping

When nodal gene is transcribed on right side of primitive streak

259
Q

What is inversus viscerum (iv)

A

Randomised left right orientation of the heart

Nodal is transcribed randomly on left or right

260
Q

True or false:

The primitive atrium is v important for atrium formation

A

False

They mainly form the auricles

261
Q

How do the definitive atria arise

What does this result in for the right?

A

Incorporation if the sinus horn (right atrium) and pulmonary veins (left atrium) to give the smooth walls of the atria

The SVC, IVC, and coronary sinus lie within the definitive right atrium

262
Q

In the embryo, all venous flow enters which part of the heart

How do they get in

A

The right sinus horn (future right atrium)

Via the SVC and IVC

263
Q

What does the left sinus horn give rise to

A

The coronary sinus

264
Q

How does oxygenated blood enter the IVC

A

Via the ductus venosus in the liver

265
Q

What is the first step in separating systematic and pulmonary circulations

A

Partial separation of the definitive atria and division of the common atrioventricular canal into right and left AV canals

266
Q

How is the total separation of systemic and pulmonary circulations achieved in the embryo

A

IT DOESNT HAPPEN

V little blood flows through the foetal lungs and blood is shunted from right to left

267
Q

How is foetal blood oxygenated

A

From the placenta, oxygenated blood enters the right atrium from the IVC and passes into the left atrium via the foramen ovale

268
Q

What does the AV canal do initially

How is it remodelled

A

Connects the primitive atrium with the left ventricle

RV increases in size, pulling canal to the right
Tissue surrounding the canal thickens forming the endocardial cushions
Endocardial cushions grow towards each other, fusing to form the septum intermedium, separating the AV canal into the left and right canals

269
Q

What do the left and right AV canals eventually form

A

The tricuspid and mitral openings

270
Q

What induces endocardial cushion formation

A

Signals from the. Myocardium

271
Q

When does the septum primum first form

What does it look like

What does it separate

A

Day 28

A thin membranous septum originating from the superior heart surface

Left and right atria

272
Q

What happens to the heart in the 5th week

A

As the Septum primum approaches septum intermedium, the ostium primum is diminished

273
Q

When is the ostium primum obliterated ?

This means blood can no longer travel from the foetal right atrium to the left atrium. True or false?

A

At the end of the 6th week

False: apoptosis occurs at the cranial end of the septum primum, forming the ostium secundum
Blood can always pass between the atria in the foetus

274
Q

Describe the septum secundum

A

A second “fence”, this time thick and muscular that descends from the roof of the right atrium, to the right of the first fence

275
Q

When does the septum secundum reach the septum intermedium?

A

It never quite reaches the septum intermedium and the remaining gap forms the foramen ovale

276
Q

Is the blood in the foetal right atrium Oxy or deoxy

A

It receives both Oxy and and deoxy from the IVC and SVC

277
Q

Describe the movement of blood through the foetal heart after the formation of the foramen ovale

A

The higher blood pressure in the right atrium pushes blood through the foramen ovale, easily pushing the flimsy septum primum open, into the left atrium to be pumped around the body

278
Q

How does the foramen ovale close

A

Closes with the newborn baby’s first breath as the abrupt dilation of pulmonary vasculature and cessation of umbilical flow increase the blood pressure in the left atrium.

This increased pressure forces the septum primum against secundum, closing the foramen ovale

279
Q

What causes atrial septal defect

A

AKA hole in the heart

If septum secundum is too short and the foramen ovale persists

280
Q

How common is ASD

What happens in the heart

What are the symptoms

A

5-10% of babies congenital heart defects

Causes left to right shunting in newborn

Generally asymptomatic but persistent increased flow to RA leads to enlarged RV and pulmonary trunk, and eventually cardiac failure in later life

281
Q

How is hole in the heart fixed?

When is surgery performed

A

Small holes can close spontaneously

Larger defects may require surgery to prevent complications

Between the ages of 3 and 5 years

282
Q

How is the muscular ventricular septum formed

A

It grows from the inferior edge of the foetal ventricle after the 4th week towards the septum intermedium. This growth halts in the middle of the 7th week, leaving an opening between the ventricles that connects to the common outflow tract (truncus arteriosus)

283
Q

When does the muscular ventricular septum begin to form?

Why does growth of the muscular ventricular septum halt in the 7th week

A

After the 4th week

Otherwise the LV would be shut off from the outflow tract

284
Q

How is septation of the heart completed

A

2 spirals form on opposite sides of the inner surface of the truncus arteriosus
The ridges spiral and fuse at inferior edge of truncus arteriosus. This fusion spreads cranially and caudally, separating the outflow tract when the spiral septum fuses inferiorly with the septum intermedium and the muscular ventricular septum

285
Q

What gives rise to the membranous ventricular septum

What does this form

A

When the spiral septum fuses with the muscular ventricular septum

The 2 separate ventricles

286
Q

What is the most common congenital heart defect?

What causes this?

What can this defect lead to?

A

Ventricular septal defect (33%)

Failure of complete fusion of the spiral septum with the muscular ventricular septum and with the septum intermedium

Tetralogy of Fallot

287
Q

How common is VSD

Which septum is it most common in

A

3/1000 live births

Membranous ventricular septum

288
Q

How severe is VSD

How can it be treated

A

Severity depends on size and position of defect

Small defects close spontaneously in 50% of cases with no long term harm
A large VSD may damage heart or lungs as it causes heart to pump inefficiently by pumping oxygenated blood through the lungs repeatedly. This leads to pulmonary hypertension
Without surgical intervention, a large VSD can lead to congestive heart failure

289
Q

What is the most common cyanotic congenital heart malformation

What causes it

A

Tetralogy of Fallot

1/1000 live births

Defect in spiral septum, which divides outflow tract into pulmonary trunk and aorta

290
Q

What is the Tetralogy of Fallot

A
  1. Pulmonary stenosis
  2. Overriding aorta
  3. Large VSD
  4. Right ventricle hypertrophy
291
Q

What is pulmonary stenosis

A

Pulmonary artery is too wide

292
Q

What is an overriding aorta

A

Aorta too wide and shifted right so receives blood from right ventricle too

293
Q

Why does hypertrophy occur in the Tetralogy of Fallot

A

The right ventricle has to work extra hard to pump blood up narrow pulmonary trunk

294
Q

When is the tetralogy of Fallot surgically repaired

A

<1 year

295
Q

Which 2 shunts allow blood to bypass the lungs

A

Foramen ovale

Ductus arteriosus

296
Q

What does the ductus arteriosus allow

A

Shunts blood from pulmonary artery to aorta to by pass the lungs

297
Q

How do the pulmonary vessels open at birth

What does this lead to

A

Pulmonary resistance drops

Closing of foramen ovale and ductus arteriosus

298
Q

When do the first and second fences fuse

A

3 months after birth

299
Q

What causes the ductus arteriosus to close

A

Reduced flow through it due to change in pulmonary circulation resistance
Reduced prostaglandin levels as maternal input is removed

300
Q

What is a PDA

How common is it

When is it more common

A

Patent ductus arteriosus

10% of congenital heart diseases

In pregnancies with persistent perinatal hypoxaemia or maternal rubella or In babies born at high altitudes or born prematurely

301
Q

What can we do to close a patent ductus arteriosus

A

Prostaglandin inhibitors

Surgery

Coil to seal it

302
Q

Why can’t we use prostaglandin inhibitors for every case of PDA

A

Only effective in the first few weeks of life

It is most important for premature babies

303
Q

How many patients with PDA die if it is not repaired

How do they die

A

1/3 by age of 40; 2/3 by the age of 60

Heart failure, pulmonary hypertension, endarteritis

304
Q

What is endarteritis

A

Inflammation of inner arterial lining

305
Q

How can you keep the ductus arteriosus patent

Why would we want to do this

A

Administration of prostaglandins

In babies with other cardiac abnormalities to keep them alive until corrective surgery

306
Q

What does the arterial system look like originally

A

With paired aorta and symmetrical pharyngeal/aortic arch arteries

307
Q

How does the venous system look originally

A

Paired cardinal veins, umbilical veins, and Vitelline veins

308
Q

How do pharyngeal/ aortic arches develop

How many arches are there

A

Sequentially - the earliest ones regressing as later ones form

5 (I-VI) but V is not present in mammals

309
Q

What does arch III form

A

Common carotid arteries

310
Q

What forms the arch of the aorta

A

Arch IV

311
Q

What forms the pulmonary trunk and the ductus arteriosus

A

Arch VI

312
Q

How is the final aortic arch

A

Initial part: truncus arteriosus
Ascendant part: aortic sac
Transverse arch: from left IV pharyngeal/ aortic arch
Descending aorta: left dorsal arch

313
Q

Which side contributes to the aorta?

What happens to the other side?

A

Left side

Right side structures regress or can be incorporated into other parts of the vascular system

314
Q

How common is coarctation of the aorta

What is it associated with

A

3/10,000 births

~5% of congenital heart defects

Valve defects

315
Q

What is coarctation of the aorta

What also is found if it is pre/ductal

What is found if it is post-ductal

A

Aortic lumen becomes significantly narrowed (from the Latin “coartare” - to press together)

Persistent ductus arteriosus

Circulation to distal body parts usually occurs through enlarged intercostals and internal thoracic arteries

316
Q

What does coarctation of the aorta cause

A

High blood pressure in arms and upper body but low blood pressure in lower body and legs

317
Q

How can you identify coarctation of the aorta

A

Different pulses in neck and groin and a distinctive heart murmur that can be heard through a stethoscope placed over the patient’s back

318
Q

How is aortic coarctation repaired?

A

A small one can be removed and the two ends anastomosed

Large ones require bypass surgery

319
Q

How common is aortic interruption

When is surgery required

A

1/10,000 births

1.3% of children with heart disease

1st year of life

320
Q

What is Type B aortic interruption

A

Caused by obliteration of left VIth arch

321
Q

For aortic interruption:

Where is Type A
Where is Type B
Where is Type C

A

A: distal to left subclavian artery
B: distal to left common carotid
C: distal to brachiocephalic artery

322
Q

Why may there be an abnormal origin of the R subclavian artery

Where is the abnormal origin

What are the symptoms?

A

Abnormal obliteration of right VIth arch, leaving distal part of right dorsal aorta

Instead of ariseung with the right common carotid as the brachiocephalic artery, it rises as its own 4th branch from the aorta, after the left subclavian artery. It hooks back to reach the right side

Asymptomatic

323
Q

Which organ greatly affects the vitelline and umbilical veins

A

Liver

324
Q

What happens to the developing vitelline veins

A

A plexus forms between the left and right veins which is then surrounded by liver cords

This gives rise to the liver sinusoids

325
Q

What happens to the left and right vitelline veins after a plexus forms between them

A

Left loses its connection to the heart and the anastomotic network develops into a single vessel: the portal vein

Right forms the hepatocardiac portion of the IVC

326
Q

When does the ductus venosus form

What does it do

A

Forms with the hepatic sinusoids

Shunts blood from the placenta (via left umbilical vein) to the IVC

327
Q

What happens to the umbilical veins

A

Left persists and anastomoses with the ductus venosus

Right is obliterated

328
Q

When do the umbilical vein and ductus venosus close

A

After birth

The obliterated ductus venosus forms the ligamentum venosum

The obliterated umbilical vein is found in the lost margin of the falciform ligament

329
Q

Congenital cardiovascular malformations accounts for how many of all congenital defects in live births and occur in how many of all live births?

A

20%

0.5-1% of all live births

330
Q

Which gene is one of the earliest genes expressed in the cardiac lineage

A

Nkx2.5

331
Q

What do you see in Nkx2.5 mutant mice

A

Absence of myosin light chain

332
Q

What does Nkx2.5 encode

A

A homeodomain transcription factor that coordinates with zinc finger transcription factors of the GATA family to activate cardiac specific genes

333
Q

When was Nkx2.5 first discovered to be required for normal heart development

How many mutations have been recorded to cause heart defects

A

In fruit flies

> 10

334
Q

Both copies of the Nkx2.5 gene need to be mutated to cause disease

A

False

It is a dominant pattern of disease inheritance - only one mutation necessary

335
Q

What do point mutations in Nkx2.5 cause

Can mutations in this gene affect adults

A

Atrial septal defects and AV conduction delays

Yes eg can cause progressive loss of AVN activity

336
Q

What gene helps valve formation from the endocardial cushions

A

Notch1

337
Q

Where do endocardial cushions form

What is this formation called

A

Where localised swellings of cardiac jelly become cellularised when endocardial cells delaminate in response to signals from the myocardium

Epithelial mesenchymal transition (EMT)

338
Q

What are the reciprocal interactions involved in the EMT

A

Between the myocardium and endocardium

339
Q

How do the endocardial cushions develop into valves

Which gene is required

Give evidence

A

They elongate to gradually form thin valve leaflets

Notch1

If Notch1 is blocked, cushions don’t form

340
Q

What causes bicuspid atrial valve

A

Notch1 mutations (only 1 copy needs to be mutated)

341
Q

Why might Notch1 mutations not become obvious until later in life

A

It is also important in preventing calcification of the valve

342
Q

What causes Alagille syndrome

What are symptoms

A

Jagged 1 mutations

Pulmonary artery stenosis and Tetralogy of Fallot (jagged 1 mutations can lead to these individually, without Alagille syndrome)

343
Q

What is Jagged 1

What does a mutation here cause

A

The ligand first the Notch receptor

Alagille syndrome: Pulmonary artery stenosis and Tetralogy of Fallot

344
Q

True or false: the heart can regenerate before birth.

A

True but it loses this ability at birth

345
Q

How can knowledge of heart development help treatment

A

Can be applied to derive cardiomyoctes from pluripotent stem cells

May also be possible to wake up dormant cardiomyocytes that are thought to exist within the heart

346
Q

Which germ layer does the kidney develop from

A

Intermediate Mesoderm

347
Q

What are the 3 stages of kidney development

A

Pronephros
Mesonephros
Metanephros

348
Q

When does the urogential ridge begin to form

In which direction?

A

Week 4

Rostral caudal direction

349
Q

When and where does the pronephos begin to develop

Is this structure essential for higher vertebrates

A

Day 24
Between somites 3-5 with the duct finding between somites 5-7

No it is a rudimentary structure but it is essential for embryonic survival of fish and amphibians

350
Q

What happens to the pronephros once it is formed?

A

Degenerates v rapidly and is never. Functional in humans

351
Q

What does mesonephros form

A

From day 28 and begins to regress at the cranial end at 5 weeks

352
Q

How many nephrotomes does the mesonephros have?

What does it produce?

A

Never more than 30

Dilute urine

353
Q

When does the ureteric bud form

A

Grows out of the mesonephric duct at 5 weeks

354
Q

What induces formation of the metanephric kidney

A

The ureteric bud

355
Q

How do the tubules in the mesonephros form

How many tubules are there

A

In cranio- caudal succession (cranial ones form first, then thoracic then abdominal)

Earlier ones degenerate as new ones form

30 tubules at any one time

356
Q

What is an important function of the mesonephros

A

Production of weak urine which maintains the composition of the amniotic fluid

357
Q

How do the metanephroi develop

A

Begins with 2 buds (the ureteric buds) which originate from the caudal end of the mesonephric duct.

These buds grow out unit the surrounding mesoderm and surrounding cells as the bud secretes signalling proteins

358
Q

How do we know the ureteric buds signal induction in surrounding cells

A

If an artificial barrier is used to prevent proteins moving between cells, development stops

359
Q

Define induction

A

Alteration of the fate of one cell type or tissue by interaction with a second

360
Q

What are the 3 phases of induction

A

Initiation
Commitment to differentiation
Morphogenesis

361
Q

Discuss the phases of induction in the example of metanephros development

A

Initiation: signals from the metanephrogenic mesenchyme induce growth of ureteric bud

Commitment: proliferation and differentiation of bud and mesenchyme (the response to the inducing signals)

Morphogenesis: in response to signals from the mesenchyme, the bud commenced branching morphogenesis and the mesenchyme responds by becoming epithelial in nature and forming nephrons

362
Q

In short, what are the consequences of induction in mesonephros development

A

Ureteric branching morphogenesis

Epithelial morphogenesis

363
Q

Describe the epithelial morphogenesis associated with metanephros development

A

Mesenchyme-epithelial transition is in response to Wnt expression

S shaped bodies form

thins on one side to form glomerulus

Fuses with ureteric bud tip

Extends to form proximal and distal tubules

364
Q

What induces outgrowth of the ureteric bud

What does it grow towards

A

GDNF secreted From the metanephric mesenchyme (MM)

Grows towards the MM

365
Q

What is GDNF

What does it bind to

A

Glial derived neurotrophic factor

Binds to Ret receptor on ureteric bud cells

366
Q

How are the renal vesicles formed

A

The metanephric mesenchyme is induced by the ureteric bud to condense around the tips of the branching ureteric epithelium and undergo a mesenchyme to epithelial transition, forming renal vesicles

367
Q

What triggers the mesenchyme-to-epithelial transition (MET)

A

Wnt9b from the ureteric tip upregulates FGF8 and Wnt4 production from the metanephric mesenchyme

This triggers (MET)

368
Q

What do the following signalling proteins do in kidney development:

a) Wnt9b
b) FGF8
c) Wnt4

Where is each secreted from

A

a) up regulates FGF8 and Wnt4 (from ureteric bud)
b) stimulates proliferation of metanephrogenic mesenchyme (from MM)
c) regulates formation and differentiation of the comma and S shaped bodies to form renal vesicles (from MM)

369
Q

What is the ampulla in the developing kidney

A

The growing tip of the branching bud

370
Q

What follows induction at the ampulla during kidney ampulla

What is this called

What does it result in

A

Another branch grows out and one nephron forms

Dichotomous branching

The regular patterning of the kidney

371
Q

What forms the collecting duct, the nephron and the convoluted tubules?

A

Collecting duct: from ureteric bud branches

The metanephrogenic mesenchyme form the nephron and convoluted tubules

372
Q

When does the mean glomerular number level off in the embryo

Is this the final number?

A

36 weeks

No some nephrogenesis and functional maturation continues after birth

373
Q

What processes form kidney blood vessels in the embryo

A

Smaller vessels are derived from vasculogenesis differentiated within the kidney

Large vessels are formed via angiogenesis- the invasion of the kidney by the renal arteries

374
Q

How common is a development abnormality in the urinary tract

A

10% of all babies

However most don’t cause problems

375
Q

When does kidney agenesis occur

A

If the ureteric bud does not reach / signal properly to the surrounding mesenchyme

376
Q

What causes poly cystic or dysplastic kidneys

A

Tubules fail to form correctly

Cells may continue to proliferate

377
Q

What probably causes double or bifurcated ureters

A

Defects in early stages of induction

378
Q

Give the mean glomerular number at 3 points in life

A

15 weeks: 15,000
40 weeks: 740,000
Adult: 617,000

379
Q

True or false:

Mean glomerular number decreases with age

A

True

380
Q

Which other disease is a decline in glomerular number related to

According to whom

Give evidence

A

Risk of hypertension

Developmental Origins of Health and Disease

Genetically induced reduction in nephron number in mice is associated with increased blood pressure

381
Q

What is nephron number in babies strongly associated with

Give a statistic

A

Birth weight

Babies with birthweight below 10th centile have 30% fewer nephrons

382
Q

What is the Developmental programming hypothesis

A

That there is a relationship between low birthweight, nephron number and hypertension

383
Q

How does the bladder form

A

The mesonephric duct and the ureteric bud both enter the posterior inferior aspect of the urogenital sinus.

In the males the mesonephric duct migrates inferiorly go enter the urethra as the vas deferens and in the female it regresses

The ureteric bud grows out and elongates you’re become the ureteric and the portion closest to the urogenital sinus splays out to generate the trigone

384
Q

What is the trigone

A

Part of the posterior wall of the bladder

385
Q

What is the urachus

What is its path

A

The connection between the developing bladder and the allantois

From the bladder to the umbilicus and the umbilical cord

386
Q

What happens to the urachus after delivery

A

It fibroses to form the median umbilical ligament

387
Q

What happens if the urachus fails to obliterate fully

A

A urachal fistula, cyst, or sinus may develop

A urachal fistula will result in urine leaking from the umbilicus

FAB (10 decks)

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