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CMMB 403 > Final 3 > Flashcards

Final 3 Flashcards

1
Q

What is the medial hinge point?

A

Collection of cells on the neural plate that have apical constriction (actin-mediated) mediate the folding of the neural tube. Brings the more lateral ectoderm toward the midline. They also anchor the notochord to the neural tube.

There are also dorsal lateral hinge points – have apical constriction - anchored to the surface ectoderm

apical constriction creates wedge shaped cells - helps promote folding.

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2
Q

What causes the neural tube to be able to separate from the overlying epithelium?

A

The cells of the neural tube begin to express different cadherins.
neural tube cells express N-cadherin while overlying cells express E-cadherin

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3
Q

What molecules are involved in specifying motor neurons?

A

SHH, PAX6, NKX6.1

Motor neurons form where the concentration of SHH is high enough to activate Nkx6.1 expression, but not high enough to inhibit Pax6 expression

Motor neurons are thus specified at moderate levels of SHH expression

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4
Q

What effect does SHH have on Pax6 expression?

A

At high concentrations, SHH inhibits or represses PAx6.

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5
Q

What effect does SHH have on Nkx6.1?

A

SHH activates Nkz6.1 at higher concentrations.

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6
Q

What type of proteins are Pax6 and Nkx6.1?

A

TF that are part of the homeodomain family

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7
Q

Which side of the neural tube do the motor neurons extend out from?

A

The ventral side

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8
Q

Which side of the neural tube do interneurons connect to sensory neurons on?

A

The dorsal side. Sensory input enters through the dorsal side of the neural tube.

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9
Q

Rhomdomeres

A

Transient structures that form after the neural tube is closed. They are compartments/segments within the hindbrain - Hox genes pattern them. Different cranial nerves are formed by these depending on the Hox genes expressed in the given region.

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10
Q

What is a structure that is formed from rhombdomere 1?

A

The cerebellum! Rhb1 is too anterior in the brain to be patterned by Hox genes

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11
Q

Which rhombdomere is the one where Hox genes begin to be present?

A

Rbd2 - Hoxa2 is expressed here. The motor neuron produced the motor neurons of the trigeminal nerve (cranial nerve that innervates your jaw)

Knockout Hoxa2 - get cerebellar expression in rbd 2

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12
Q

What is the germinal epithelium?

A

When the neural tube fuses, the tube consists of a single layer of cells that become/are neural stem cells - this layer is called the germinal epithelium

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13
Q

What part of the brain forms from the telencephalon of the forebrain?

A

the cerebrum (conscious thought, complex)

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14
Q

What part of the body forms from the diencephalon of the forebrain?

A

The retina

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15
Q

What brain structures develop from the hind brain?

A

cerebellum, pons, medulla

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16
Q

About how many cells are there in our brain?

A

~170 million. About equal amounts of neurons and support cells.

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17
Q

When do neural crest cell begin their migration?

A

Day 22

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18
Q

How is the migration of neural crest cells determined?

A

Migration is directed by attraction (chemotaxis) and repulsion mediated by proteins such as ephrins and their receptors.

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19
Q

What day is when all of the neural crest cells have at least begun their migrations?

A

Day 29

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20
Q

Which proteins are neural crest cell specifiers?

A

Moderate BMP levels, and the transcription factors FoxD3, Snail, and Slug

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21
Q

What do Snail and Slug do?

A

These are transcription factors that assist in specifying neural crest cells. They repress the expression of E-cadherin to promote the epithelial to mesenchymal transition that NCC undergo.

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22
Q

What is the exception to ‘All of the PNS is formed by NCCs)?

A

Ectodermal placodes form some parts of sensory neurons

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23
Q

Which pigment in the body does not come from neural crest?

A

The pigment in the retina

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24
Q

Where are NCCs responsible for bone formation?

A

Only in the skull and face. NCCs do not form bone anywhere else in the body.

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25
Q

Which somite levels are where the vagal and sacral neural crest migrates from?

A

Vagal: Somites 1-7 (anterior)
Sacral: Posterior to Somite 28

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26
Q

Where somite levels does the trunk neural crest migrate from?

A

Somites 18 - 24

There are 2 pathways of migration

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27
Q

Which somite levels does the cranial neural crest migrate from?

A

Anterior to the somites!

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28
Q

Where somite levels does the cardiac neural crest migrate from?

A

Overlaps with the vagal neural crest - somites 1-7

Somites 1,2,3

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29
Q

Where do vagal and sacral neural crest migrate to?

A

Both of the populations migrate into the gut. They migrate to form the enteric NS

  • The need GDNF to be expressed from the gut endoderm in order for their migration to be successful
  • These cells express RET (an RTK) on their cell membranes - mediate the migration
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30
Q

GDNF

A

glial-derived neutrophic factor
A secreted molecule released from the gut endoderm cells. Production of this factor is necessary for the successful migration of vagal and sacral neural crest cells to this region.
RET is the receptor (RTK) for the GDNF

also secreted by the metonephrogenic mesenchyme to stimulate the uretic bud to bud

GDNF here also stimulates Wnt11 expression in the tips

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31
Q

Hirschprungs disease

A

haploinsufficient phenotype
Results of there is either not enough RET (RTK) or GDNF (ligand) expressed to mediate the migration of vagal and sacral NCCs to the gut region.

Failure of cell migration to the colon
Get insufficient peristalsis (reduced/absent) due to reduced enteric neurons

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32
Q

What is Pathway 1 of trunk neural crest cell migration?

A

Earlier than Pathway 2

  • cells migrate to become dorsal root and sympathetic ganglia, and the adrenal medulla
  • sensory, sympathetic, and parasympathetic neurons

These cells migrate only through the anterior regions of the sclerotome part of each somite.

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33
Q

Where is the adrenal cortex from?

A

Intermediate mesoderm

Adrenal MEDULLA (from the trunk NCC-Pathway1)

34
Q

Pathway2 Trunk NCC

A

Begin migration slightly later than Pathway 1
They migrate between the epidermis (ecto) and dermis (meso) all throughout the body.
Become the melanocytes (pigment)

The NCCs in this pathway express a RTK called Kit. The cells of the dermis secrete a stem cell factor ligand which signals to the NCC (via Kit) to keep them alive and migrating correctly.

Activation of this signalling pathway also turns on melanocyte genes. MITF, a TF is phosphorylated by ERK as a result of the signalling, which helps to turn on melanoblast specific genes

35
Q

Where are the dorsal root ganglia?

A

They are located just laterally outside of the spinal cord. There is a dorsal root ganglion in between every vertebral bone, on both sides of the vertebra.

36
Q

Spinal nerves

A

Exit between each vertebra, on both sides of the spinal cord. Consist of bundles of both sensory neurons (IN) and motor neurons (OUT)

37
Q

What are ephrins?

A

Ephrins are membrane-bound ligands for a RTK receptor called the ephrin protein/molecule.

Ephrins are attached to cell membranes in the POSTERIOR SCLEROTOME

The trunk neural crest cells (migrating through the anterior sclerotome express the ephrin protein (RTK) – this promotes a repulsion - allows the NCC to remain on their path of migration.

38
Q

Boundary formation in the trunk NCC of pathway 1

A

NCC migrate through the anterior sclerotome of the somites and express the receptor, the ephrin protein (RTK) on their cell membrane

Cells in the posterior sclerotome of somites express the membrane-bound ligand, ephrin. The interaction between these two is repulsive, like grabbing an electric fence.

Where these molecules meet and bind creates these borders and allows the NCCs to remain on their path of migration

39
Q

What structure forms from the NCCs that remain in the sclerotome?

A

Dorsal root ganglia

40
Q

Motor neuron growth cone repulsion

A

Motor neuron axon extension occurs similarly to NCC migration.
The growth cones at the tip of the motor neurons express ephrin proteins (RTK) and are guided through the anterior sclerotome (more ventrally) as the posterior sclerotome has ephrin ligand (repressive)

41
Q

How does the Kit - stem-cell factor signalling play a role in NCC migration?

A

Kit is an RTK receptor on the trunk pathway 2 NCC. Kit binds to the stem cell factor ligand that is produced by dermis cells

This signalling ensures that the NCCs stay alive at that their migration is successful.

This signalling also activates melanocyte-specific genes (MITF, a TF is phosphorylated and activated by this signalling)

42
Q

MITF

A

A TF that is activated by the activation of the RTK pathway (Kit and stem cell factor) in NCC that are going to be melanoblasts

Turns on melanocyte specific genes

if there is not enough signalling (ie lack of Kit, stem cell factor, or MITF - don’t get sufficient pigment on the ventral side of the body.

43
Q

What germ layer is/are pharyngeal arches composed of?

A

Ectoderm (NC and surface) and mesoderm

Each of the pharyngeal arches has an associated cranial nerve

44
Q

What does the first pharyngeal arch develop into?

A

Mandible and Maxilla (jaws)

Humans have 5 pharyngeal arches (1,2,3,4,6)

45
Q

Where do the bones of the middle ear come from?

A

The first 2 pharyngeal arches. These bones are derived from cranial NCC

46
Q

Which bones of the skull are derived from cranial neural crest?

A

facial bones, frontal bone, and the interparietal bone

The parietal and temporal bones are from paraxial mesoderm

The skull has a dual origin

47
Q

Where does the cardiac NC arise from spatially?

A

Just posterior to where the otic placode is
Migrates to form the outflow tract of the heart

Migrate through pharyngeal arches 3,4,6

48
Q

Where does the bulk of the heart come from?

A

lateral plate mesoderm

49
Q

Which structures form from the intermediate mesoderm?

A

Kidneys, gonads

Sertoli & theca cells

50
Q

What structure is derived from the chorda-mesoderm?

A

The notochord

51
Q

what stuff forms from the paraxial mesoderm?

A

Head, somites (sclerotome, myotome, dermatome, syndatome, endothelial cells

parietal bone, temporal bone

52
Q

Lateral plate mesoderm

A

Splanchnic (circulatory system), somatic (body cavity), extraembryonic

53
Q

Which signals are involved in somitogenesis?

A

Fgf8 and Notch signalling
Fgf8 must be below a certain threshold for somites to form

cyclic activation of Notch signalling and downstream genes (this sets the timing and location of somite separation from the PSM)

*Notch signalling activates the lunatic fringe gene (neg feedback)

54
Q

When do the first somites appear? When is somitogenesis complete?

A

Day 20-Day 30

55
Q

How many cell are there per kidney? Per nephron?

A

1 million nephrons per kidney and 10 000 cells per nephron

56
Q

Which kidney structure is the functioning kidney in fish and amphibians?

A

Mesonephros. Linear array of thousands of nephrons

In humans, the mesonephros typically consists of 20-40 neurons

57
Q

What type of tissue is the surrounding mesenchyme in kidney development?

A

Also intermediate mesoderm

58
Q

ureteric bud

A

Initial bud off of the metanephric duct. It buds and branches into the surrounding mesenchyme

A condensate of mesenchymal cells form at the tips and undergo a mesenchymal to epithelial transition to become a continuous tube - the nephron

The growth of this bud is dependent on signalling with GDNF and Ret

59
Q

What does the mesenchyme secrete that causes the ureteric bud to branch?

A

GDNF is released from the mesenchymal cells and this stimulates the uretic bud to extend and branch because the metonephroduct/wolffian duct epithelia here expresses the RET (RTK) receptor in high concentrations.

60
Q

What do the Hox11 paralogs do in kidney development?

A

They induce GDNF expression by the metanephrogenic mesenchyme
No kidneys will develop if the Hox 11 paralogs are knocked out.

GDNF is haplonsufficient

61
Q

How are Wnts involved in kidney development?

A

After the GDNF induces the initial budding…
Wnt9b is expressed in the stalk of the bud (not in the tips) - this is secreted and induces the surrounding mesenchyme to condense around it (~20 cells)

The condensed mesenchyme than induces the tips of the bud to express and secrete Wnt 11
Wnt11 is expressed at the tips and triggers branching.

The new branches express Wnt 9b, which induces more mesenchymal condensation - cycle repeats.

Within the condensing mesenchyme, Wnt4 is required. In an autocrine fashion, Wnt 4 is released and stimulates MET

62
Q

Function of each Wnt in kidney formation

A

Wnt 9b - expressed on the stalks - induces condensation of mesenchyme at the tips
Wnt11 - expressed at the tips - induces branching to occur
Wnt 4 - condensed mesenchyme cells at tips will then express Wnt 4 which stimulates, in an autocrine fashion, for these cells to undergo MET and form an epithelium (neurons)

63
Q

What molecules specify cardiogenic mesoderm?

A

Wnt inhibitors, FGF8, and BMPs, Nkx2.5

Splanchnic lateral plate mesoderm develops in close association with the underlying endoderm

These are expressed from the underlying anterior endoderm

64
Q

What body structures form from the somatic lateral plate mesoderm?

A

limb buds and limb bones

in close association with the overlying ectoderm

65
Q

When does the heart specification and beating start?

A

The lateral ruminents of the heart are specified at Day 20

Heart is beating by day 22

66
Q

What is the heart formed from?

A

From two cardiac rubes which are formed from the splanchnic lateral plate mesoderm

Get heart where there is high BMPs and high Wnt inhibitors (laterally)

67
Q

How does Crescent play a role in specification of heart cells?

A

Crescent is a wnt inhibitor that is expressed in the entire anterior region of the early embryo

68
Q

Where is Nkx2.5 expressed? What does it do?

A

It is expressed in the cardiac crescent. Wnt inhibitors activate its expression.
It is a TF necessary for activating cardiogenic genes
specifier of the heart
It is expressed where there is high BMP and low Wnt (high Wnt inhibitors)

BMPs, wnt-inhibitors, and Fgf8 - activate Nkx2.5

69
Q

Specification of lateral plate mesoderm to become cardiogenic

A

Anteriorly, the lateral plate mesoderm is exposed to low Wnt signalling because dikkopf and crescent are present (Wnt-inhibitors). BMPs and FgF-8 - high

70
Q

What does retinoic acid have to do with heart formation?

A

The posterior part of the heart is exposed to higher RA levels (enzyme that converts retinol to RA is high here) - this specifies this region to be the inflow or venous portion of the heart, the atria!

The ventricles will come from the more anterior part…

71
Q

What does heart looping do?

A

RA specifies posterior part of heart to become atria and the ventricles are more anteriorly specified - must be flipped so the atria are anterior
Looping is always to the right!
Day 23-28

72
Q

Which molecules are necessary for the direction of looping?

A

Nodal and Pitx2 - to the RIGHT in normal idvls.

73
Q

What do vegetal cells become in xenopus?

A

Endoderm

These cells induce the cells above them to become mesoderm.

74
Q

VegT

A

MEG

When expressed, Veg protein is a TF that promotes expression of Nodal-Related genes - promotes phosphorylation of Smad2

75
Q

What signals are required to induce mesoderm formation in Xenopus?

A

MEG - VegT and Vg1 - located vegetally

VegT - translated - VegT protein is a TF that activates the expression of genes required for the formation of the mesoderm. Including Nodal-related ligands!

Vg1 - a nodal-related ligand (when a protein). The mRNA is translated DORSALLY. Not a TF

76
Q

What signals cause the ventral mesoderm to form?

A

low Nodal-related signalling and no stabilized B-catenin.

77
Q

Examples of Wnt-inhibitors?

A

Cerberus, Frisbee, Dikkopf

78
Q

What is the Niewkoop centre?

A

It is the source of signals that induces the organizer to form
In zebrafish, it is the yolk syncytial layer below the embryonic shield

Nodal like +Wnt signals

79
Q

Definition of colinearity

A

The order of the genes along the chromosome/complexes correlates with their function along the anterior to posterior axis

The physical order of Hox genes along a chromosome correlates with their anterior expression limit in the embryo (spatial colinearity) and with their order of activation during development (temporal colinearity)

The functioning of a Hox gene is also typically within its most anterior region of expression.

80
Q

hox gene fact

A

The anterior region where a Hox gene is expressed is usually where its patterning function is most important

CMMB 403 (7 decks)

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