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Embryology > Gastrulation > Flashcards

Gastrulation Flashcards

1
Q

During week 2, how do the cells of the blastocyst further differentiate?

A

Trophoblast:

  • cytotrophoblast - an inner layer of mononucleated cells
  • syncitiotrophoblast - an outer layer of multinucleated cells that lack distinct cell boundaries

Embryoblast:

  • Hypoblast - small cuboidal cells adjacent to the blastocyst cavity
  • Epiblast - high columnar cells adjacent to the amniotic cavity
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2
Q

After further differentiation of the trophoblast and embryoblast, what structure is formed?

What cavity appears?

A

the flat bilaminar disc is formed from the hypoblast and epiblast

  • at the same time that this disc is formed, the amniotic cavity appears within the epiblast
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3
Q

What are the 3 key roles of the syncytiotrophoblast?

A
  • immune protection
  • production of hCG
  • formation of the placenta
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4
Q

What is meant by trilaminar disc formation?

Which cell type is responsible for this?

A

gastrulation involves the formation of a trilaminar disc which contains the 3 primary germ cell layers

  • the epiblast will give rise to:
    • ectoderm
    • mesoderm
    • endoderm
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5
Q

What is meant by gastrulation and when does it occur?

What other systems start to develop around the same time?

A
  • gastrulation occurs during week 3
  • it involves establishing 3 primary germ cell layers from which all body systems will develop
  • the vascular system and neural plate / neural tube also start to develop during week 3
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6
Q

What else does gastrulation allow the establishment of?

A
  • gastrulation allows the establishment of the 3 body axes:
  • cranial-caudal axis
  • right-left axis
  • dorsal-ventral axis
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7
Q

What can cause disruption to gastrulation and what can this lead to?

A
  • aberrant gastrulation can be caused by genetic mutations / abnormalities or maternal toxins
  • at the start of gastrulation, epiblast cells are “fate-mapped”
    • the cells have a set destination as to what type of cell they will differentiate into
  • gastrulation is highly sensitive to insults, which can cause catastrophic coongenital abnormalities as body axes are being established during this process
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8
Q

What is the major change that takes place in the embryo between the 2nd and 3rd weeks?

A

During week 2:

  • the ICM is separated into 2 layers - the epiblast and hypoblast
  • these 2 layers together make up the bilaminar disc

During week 3:

  • the bilaminar disc becomes a 3-layered trilaminar disc through the process of gastrulation
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9
Q

What are the 3 layers of the trilaminar disc?

A
  • ectoderm
  • mesoderm
  • endoderm
  • these 3 layers will give rise to all the tissues of the embryo
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10
Q

What structure marks the beginning of gastrulation?

Why is this important in laterality?

A
  • gastrulation begins with the formation of the primitive streak on the surface of the epiblast
  • this consists of the primitive pit, node and groove
  • the primitive node is important in laterality as it contains cilia cells that sweep cells in certain directions
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11
Q

How does formation of the primitive streak establish body axes?

What happens following its formation?

A
  • formation of the streak divides the embryo into right and left sides and establishes this body axis
  • the epiblast cells detach and migrate through the primitive streak
  • the first layer of epiblast cells to invaginate into the streak settle to form the endoderm
  • the second wave of migrating cells form the mesoderm
  • the remaining epiblast cells do not migrate and form the ectoderm
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12
Q

Which signalling factors are important in formation of the trilaminar disc?

A
  • cell migration and specification is controlled by FGF8, synthesised by cells of the primitive streak
  • FGF8 controls cell movement by downregulating E-cadherin, which usually binds the epiblast cells together
  • FGF8 controls cell specification in the mesoderm by regulating BRACHYURY expression
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13
Q

When does the primitive streak regress?

What does it do during this process?

A
  • it is a transient structure that begins to regress after the epiblast cells have migrated through
  • it lays down cells beneath it as it regresses
  • the cells located most dorsally will form the notochord
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14
Q

What are the 3 body axes and when do they start to be established?

A
  1. anteroposterior (craniocaudal)
  2. left-right
  3. dorsoventral
  • establishment of the body axes occurs prior to gastrulation
  • the A-P and D-V axes are established before the L-R and probably during the morula stage
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15
Q

Which axis is determined during the blastocyst stage?

Which region of the embryo is important in formation of this axis?

A

anteroposterior (A-P) axis

  • cells destined to form the anterior visceral endoderm (AVE) at the cranial end of the endoderm layer of the bilaminar disc migrate towards the head region
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16
Q

What genes are expressed by cells of the anterior visceral endoderm (AVE)?

A
  • the cells of the AVE express genes that are essential for head formation, including transcription factors:
  1. OTX2
  2. LIM1
  3. HESX1
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17
Q

What secreted factors are produced by cells of the anterior visceral endoderm (AVE) and what is their role?

A
  1. cerberus
  2. lefty1
  • these factors (both part of the TGF-B family) inhibit nodal activity (TGF-B) in the cranial region of the embryo
18
Q

How is the dorsal end of the embryo established during the blastocyst stage?

A
  • the absence of cerberus and lefty1 at the caudal end allows nodal expression to continue
  • nodal establishes and maintains the primitive streak
  • once the streak has formed, nodal upregulates a number of genes responsible for formation of dorsal and ventral mesoderm and head / tail structures
19
Q

What is the role of HNF-3B?

A
  • it maintains the primitive node
  • later it induces regional specificity in the forebrain and midbrain regions
  • without HNF-3B, embryos fail to gastrulate properly and lack forebrain and midbrain structures
20
Q

Where is BRACHYURY expressed?

What are its 2 main roles?

A
  • expressed in the primitive node and notochord
  • it controls formation of dorsal mesoderm in the middle and caudal regions of the embryo
  • it is responsible for cell migration through the primitive streak
21
Q

What can the absence of BRACHYURY result in?

A

caudal dysgenesis

  • as BRACHYURY is important for mesoderm formation in the middle and caudal regions of the embryo, its absence results in shortening of the embryo
22
Q

What other 3 factors rely on BRACHYURY expression?

A
  • nodal
  • lefty1
  • lefty2
23
Q

What is secreted by the primitive streak that is involved in establishing laterality (left-right sidedness)?

A
  • when the streak appears, cells in the streak and node secrete FGF8
  • FGF8 induces expression of nodal
  • nodal expression is restricted to the left side by the accumulation of serotonin (5-HT) on the left side
24
Q

What is the result of high concentrations of serotonin (5-HT) on the left?

A
  • high concentrations of 5-HT activate the transcription factor MAD3
  • MAD3 restricts nodal expression to the left side of the primitive streak
25
Q

Why is serotonin concentrated on the left side of the primitive streak?

What happens if this balance is disturbed?

A
  • it is concentrated on the left side as it is broken down by monoamine oxidase (MAO) on the right side
  • abnormal / disturbed serotonin signalling can lead to laterality defects
26
Q

What 3 midline genes are responsible for establishing laterality?

A
  • SONIC HEDGEHOG (SHH)
  • LEFTY1
  • ZIC3
  • these are all involved in establishing the midline as well as _preventing *NODAL* expression from crossing over_ to the right side
27
Q

What is the ultimate result of nodal protein being present in the left lateral plate mesoderm?

A
  • nodal protein initiates a signalling cascade that includes activation of LEFTY2
  • LEFTY2 then upregulates / induces PITX2
  • PITX2 is a homeobox-containing transcription factor that acts as a “master gene” responsible for establishing left-sidedness
  • PITX2 is expressed on the left side of the heart, stomach and gut primordia as they assume their normal asymmetric body positions
28
Q

What can happen if there is ectopic expression of PITX2?

A

laterality defects

  • if it is expressed on the right side, this results in conditions such as situs inversus and dextrocardia
29
Q

Whilst genes regulating right-sided development are less well-defined, which one is known to be involved?

A

SNAIL

  • this is a transcription factor that is restricted to the right lateral plate mesoderm
  • it is thought to regulate effector genes responsible for establishing the right side
30
Q

What is caudal dygenesis and why does it occur?

A
  • also known as sirenomelia or “mermaid syndrome”
  • insufficient mesoderm is formed in the caudalmost region of the embryo
  • mesoderm contributes to formation of the lower limbs, urogenital system and lumbosacral vertebrae, so there are abnormalities in these structures
  • a single fused lower limb is seen with an absent genitourinary system
31
Q

Why does caudal dysgenesis occur?

What signalling factors could potentially be involved?

A
  • abnormal cell migration occurs due to:
  1. premature regression of the primitive streak
  2. insufficient migration of epiblast cells

the germ layers are formed in a cranial-caudal fashion, so the head end is formed but the tail end is not

  • NODAL and BRACHYURY are important in maintaining the streak, so it is likely to be a problem with one of these signalling factors
32
Q

What is the treatment for sirenomelia?

A
  • it is difficult to treat as you are trying to create systems / limbs out of tissue that has failed to form correctly
33
Q

What is holoprosencephaly (HPE)?

How does a child with this condition present?

A
  • HPE results from disruption and death/loss of cells in the midline during gastrulation
  • the forebrain is small and the 2 lateral ventricles often fuse to form a single ventricle
  • the eyes are close together or fused (hypotelorism)
  • it affects the cranial region - tissue has formed but there has been excessive apoptosis of cells in the midline
34
Q

What toxin is known to be associated with HPE?

What signalling factors could potentially be involved?

A
  • high doses of alcohol during gastrulation (start of 3rd week) can disrupt the process and kill cells in the anterior midline of the trilaminar disc
  • this produces a deficiency of the midline in craniofacial structures
  • SHH and HNF-3B may be involved, but signalling factors are not necessarily involved
35
Q

How can a teratoma result from abnormal gastrulation?

A
  • remnants of the primitive streak persist in the sacrococcygeal region
  • there is continuous migration of epiblast cells through the streak
  • the epiblast cells are pluripotent so will proliferate and differentiate into structures formed from all 3 germ layers
  • teratomas also formed by PGCs migrating to extragonadal sites
36
Q

What is situs inversus?

How might someone present and what are the associated risks?

A

a condition where the positioning of all organs is reversed in a mirror image arrangement

  • individuals with this condition are not at high risk for other congenital abnormalities
  • their progeny is at higher risk of having a laterality defect and an even higher risk of a cardiac malformation
  • 20% of patients have Kartagener syndrome (bronchiectasis and chronic sinusitis due to abnormal cilia)
37
Q

What is situs ambiguous?

Why does it occur?

A

a condition in which one or more organs are abnormally reversed in position

  • it is a laterality defect that results from failure to establish the L-R axis
38
Q

How can you tell if someone with situs ambiguous is predominantly right or left-sided?

A
  • those with left-sided bilaterality have polysplenia
  • those with right-sided bilaterality have asplenia** or a **hypoplastic spleen
39
Q

What risks are associated with having situs ambiguous?

A
  • individuals are at a higher risk of having other birth defects, such as:
    • midline malformations
    • neural tube defects
    • cleft palate
    • anal atresia
  • 90% will have a congenital heart defect
40
Q

Why are SSRIs sometimes contraindicated in pregnancy?

A
  • serotonin (5-HT) is important in establishing laterality
  • disrupting 5-HT signalling can result in situs inversus, dextrocardia, situs ambiguous and many heart defects
  • there is an increased risk of heart defects and other congenital malformations if SSRIs are taken during pregnancy

Embryology (20 decks)

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