Lecture 10: Organogensis Flashcards

1
Q

What is organogenesis?

A

The process of formation of specific organs and related structures during development

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2
Q

Organogenesis can be used as a model system to study what developmental processes?

A

Specification

Axis and pattern formation

Induction

Morphogenesis

Cellular differentiation

The mechanisms involved are very similar to the ones in earlier development

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3
Q

Specification of germ layers

An unfertilized amphibian egg has polarity among animal and vegetal poles.

What do each of these give rise to?

Animal pole blastomere
Vegetal pole blastomere
Equatorial blastomere

A

Animal pole blastomere = ectoderm

Vegetal pole blastomere = endoderm

Equatorial blastomere = mesoderm

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4
Q

Specification of germ layers

What are the two major functions of vegetal cells?

What is this process called?

A

Differentiate into endoderm

Induce equatorial cells to become mesoderm

BOTTOM-UP SPECIFICATION

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5
Q

Specification of germ layers

Sperm entry sets up what axis?

A

the D-V axis

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6
Q

Where is the dorsal side relative to the site of sperm entry?

A

On the opposite side

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7
Q

What are dorsalizing factors?

A

form a signalling centre in DV axis

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8
Q

Generating A-P axis in Drosophila

Summary of all the genes

A

Pattern established by MATERNAL EFFECT GENES —> form gradients and regions of MORPHOGENS (transcription factors)

These morphogens activate the GAP GENES –> define broad territories of the embryo

The gap genes lead to expression of PAIR RULE GENES –> divide the embryo into periodic units

Transcription factors encoded by the pair-rule genes SEGMENT POLARITY GENES –> divide the embryo into segment-sized units along the anterior-posterior axis

All combined = regulate HOMEOTIC GENES that define identities of each of the segments

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9
Q

Generating A-P axis in Drosophila

What is an example of maternal effect?

A

Bicoid

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10
Q

Generating A-P axis in Drosophila

What is an example of gap genes?

A

Hunchback and Kruppel

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11
Q

Generating A-P axis in Drosophila

What is an example of pair-rule gene?

A

Fushi tarazu

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12
Q

Generating A-P axis in Drosophila

What is an example of segment polarity gene?

A

Engrailed

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13
Q

Generating A-P axis in Mammals

The mammalian embryo has how many two signaling centers. What are they?

A

The node

Anterior visceral endoderm (AVE)

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14
Q

Generating A-P axis in Mammals

The mammalian embryo has how many two signaling centers.

One of them is the node. What is it responsible for?

A

The node is responsible for neural induction and patterning of AP axis

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15
Q

Generating A-P axis in Mammals

The mammalian embryo has how many two signaling centers.

One of them is the Anterior Visceral Endoderm (AVE). What is it responsible for?

A

position of the primitive streak

similar to the head portion of the amphibian organizer

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16
Q

Generating A-P axis in Mammals

AVE and therefore the A-P axis are likely generated by

A

the shape of the uterus such that the growth occurs in one direction

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17
Q

Generating A-P axis in Mammals

A-P axis is dependent on what to regulate the activity of Hox genes?

A

concentration gradients of BMPs, Wnts, FGFs, Retinoic acid etc

18
Q

Generating A-P axis in Mammals

______ are homologous to the homeotic genes of Drosophila (highly conserved)

A

Hox genes

19
Q

Generating left-right axis in mammals

Placement of the organs in humans is determined along the left-right axis

It works through what?

A

works through gradients of BMP, Shh, Nodal and Pitx2 etc.

20
Q

What did Spemann’s experiment show the concept of?

A

nuclear equivalence

we know a lot more about the DV axis because this was one of the earliest studies

21
Q

Spemann-Mangold organizer

Describe the experiment with newts.

A

Fertilized egg and tied along the first plane of cleavage –> nuclear division was constricted to one side (only dividing on one side bc other side had no nucleus)

The nucleus could migrate to the other side

As soon as the nucleus went there, cleavage would start and growth

They found development of twin larvae (one was more developed than the other)

22
Q

Spemann-Mangold organizer

Describe the experiment with amphibians.

A

Showed the concept of asymmetry!

A. Made constriction on amphibian egg so that each cell gets some gray crescent and then separate two isolated cells

B. Made constriction on amphibian egg so that one cell gets all the gray crescent and then separate the isolated cells

RESULT: if there was no gray crescent, formation of a belly piece resulted (lack of dorsal structures)

23
Q

Spemann-Mangold organizer

Later fate mapping experiments showed that gray crescent cells give rise to what?

A

the dorsal lip of the blastopore

24
Q

Spemann-Mangold organizer

Dorsal lip cells are ________ to invaginate into the blastula to initiate gastrulation

A

committed

25
Q

Spemann-Mangold organizer

Further experimentation: cells of early gastrula were uncommitted and went through conditional specification whereas cells of late gastrula

A

were determined and went through autonomous specification

26
Q

Spemann-Mangold organizer

Describe the experiment that showed the only the dorsal lip of the blastopore has autonomous determination int eh early gastrula?

A

Experiment: Transplant dorsal lip between embryos of two differently pigmented species (dorsal lip –> ventral epidermis (belly skin))

27
Q

Spemann-Mangold organizer

Dorsal lip cells and their derivatives (notochord and head endo-mesoderm) were called

A

organizer

established the basic body plan

28
Q

Spemann-Mangold organizer

What happens when cells are at the right place at the right time?

A

convergence of two signals

29
Q

Spemann-Mangold organizer

Cell right place, right time

Convergence of two signals

First signal tells the cells that they are _____

Second signal tells the cells that they are _____

Interaction of these signals does what?

A

First signal tells cells they are dorsal (dorsal signal)

Second signal tells cells they are mesodermal (vegetal signal)

Interaction of these signals creates polarity within mesoderm –> basis for specifying the organizer and forming D-V polarity

30
Q

What is the organizer induce by?

A

The Nieuwkoop Centre

31
Q

What is the Nieuwkoop Centre?

A

It induces the organizer

The dorsal vegetal cells of the blastula that can induce the overlying tissue to become the organizer

32
Q

The dorsal signal – role of β-catenin

Upon sperm entry, what happens?

A

Upon sperm entry,

microtubules get organized and corticol rotation takes place

Enables translocation of Dsh protein and Wnt11 RNA
- slow by emans of cortical roation (Wnt11)

Fast transport by means of motor protein kinesin and microtubules (Dsh-GBP complex)

33
Q

Wnt11, Dsh and GBP accumulate on the opposite side of the sperm entry, leading to

A

stabilization / accumulation of β-catenin on dorsal side

34
Q

Where does β-catenin accumulate?

A

on the dorsal side

35
Q

What activates the genes that are necessary for the formation of the D-V axis?

A

β-catenin and Tcf3 complex

36
Q

The Vegetal Signal

Vegetal region has an accumulation of maternal mRNA for TFs called

A

VegT and Vg1

37
Q

What is the role of VegT?

A

VegT –> Sox17 –> activates genes necessary to specify the cells to become the endoderm

38
Q

What does VegT also activate?

A

VegT also activates Nodal (TGF-β family paracrine factors) –> induce the cells above to become mesoderm

39
Q

What does Nodal activate?

A

accumulation of phosphorylated Smad2 —> activates eomesodermin (eomes) and Brachyury (Xbra) genes —> specification as mesoderm

Eomes + Smad2 —> activate zygotic VegT i.e. switch to zygotic mRNA from maternal

40
Q

Combination of β-catenin (Wnt signalling) and VegT/Vg1 (TGF-β / Smad signalling) activates

A

Xnr (Xenopus nodal-related) genes —> gradient of Xnr proteins (highest in the dorsal region)