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NEUR 310 > Neurulation > Flashcards

Neurulation Flashcards

1
Q

How is the blastula formed?

A

The blastula is an agglomeration of cells and fluids that results from a series of mitotic divisions.

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2
Q

True or false: at the stage of blastula formation, cell fates are already determined.

A

True (can be dyed).

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3
Q

Which part of the blastula eventually forms the nervous system?

A

The dorsal lip of the blastopore.

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4
Q

What happens at the developmental stage of gastrulation?

A

The vegetal pole of the blastula invaginates (rearrangement from the exterior to the interior), giving rise to a multi-layered structure.

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5
Q

What are the three germ layers defined following gastrulation? Which one eventually forms the nervous system?

A

Ectoderm (eventually forming the NS), mesoderm and endoderm.

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6
Q

At what stage of the development are the rostral-caudal and dorsal-ventral axes defined?

A

At the end of gastrulation.

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7
Q

What is the process of neurulation referring to?

A

The process by which the inward migration of the neural plate forms the neural tube.

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8
Q

What can arise from an improper closure of the neural plate?

A

Congenital birth defects such as Spina Bifida.

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9
Q

Why have Spemman and Mangold named the dorsal lip of the blastopore “the organizer”?

A

In a transplant experiment, Spemman and Mangold showed that transplanting a second dorsal lip of the blastopore to a host embryo was sufficient to “dorsalize” its ventral region, meaning that the dorsal lip of the blastopore is sufficient to induce a change in cell fate, to “organize”.

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10
Q

Give an example of neural induction.

A

The dorsal midline of the mesoderm induces the overlying ectoderm to become the neural plate.

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11
Q

Why did Toivonen and Wartiovaara propose that the dorsal lip of the blastopore secretes neuralizing factors?

A

Placing a filter between an explant of the dorsal lip of the blastopore and an explant of ectoderm does not prevent the former from inducing formation of neural structures in the latter, hinting at the fact that induction results from secretion and not from cell-to-cell interactions.

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12
Q

Why did Grunz and Tacke propose that the neural identity is actually the default fate of ectoderm cells?

A

If ectoderm cells are grown apart from each other in vitro, they develop a neural fate, suggesting that cell-to-cell interactions inhibit the default neural fate.

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13
Q

What signal originally inhibits the neural fate of ectodermal cells?

A

BMP-4 signaling.

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14
Q

To what kind of receptors are BMP ligands binding to?

A

RTK receptors.

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15
Q

Provide 3 lines of evidence that BMP inhibits the “default” neural fate.

A
  1. Blocking BMP signaling leads to formation of two dorsal axes.
  2. BMP can cause dissociated ectodermal cells to become epidermal.
  3. BMP binding to ectodermal cells induces expression of epidermal-related genes.
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16
Q

How are Noggin, Chordin and Follistatin collectively referred to?

A

As neural “inducers”.

17
Q

What region of the blastula secretes the neural inducers?

A

Dorsal lip of the blastopore (DLB).

18
Q

What is the advantage of having many signals inducing the neural fate?

A

Significantly increase the success rate of the process.

19
Q

How what Noggin discovered?

A

Synthetic mRNAs made from the cDNA library of the dorsal lip of the blastopore were injected by trial and error in embryos with UV-induced ventralization until Noggin, a molecule sufficient to induce dorsalization by itself, was isolated.

20
Q

How can a biological dye serve as evidence to the claim that Noggin is a neural inducer?

A

Staining Noggin reveals that it is mainly expressed in the dorsal mesoderm and in the organizer.

21
Q

How was Chordin discovered?

A

Hybridization of UV-irradiated ventralized and LiCl-treated dorsalized embryos allowed to identify cDNAs only expressed in dorsalized embryos and further investigate their functions.

22
Q

What could be three lines of evidence for the characterization of a neural inducer?

A
  1. Injection of molecule is sufficient to dorsalize a region of the blastopore.
  2. Highly expressed in the organizer and its surround regions.
  3. Induces expression of neural markers.
23
Q

How are neural inducers inhibiting BMP signaling?

A

Neural inducers are competing with BMP by binding to BMP-specific RTK receptors.

24
Q

Is it fair to say that the organizer directly induces neural fate?

A

No, the organizer is actually relieving BMP’s inhibition of neural fate.

25
Q

What does determine whether neural tissue becomes rostral or caudal? Provide examples.

A

It depends on its neural inducers. For example, the segment of the neural plate induced by Chordin, Noggin and Follistatin give rise to the most rostral structure. Alternatively, the segment of the neural plate induced by FGFs and retinoic acid give rise to the most caudal neural tissue.

26
Q

What genes are of particular interest for the establishment of the rostral-caudal axis? What are they coding for?

A

Hox genes. Coding for transcription factors.

27
Q

What is the Hox Code?

A

The Hox Code is the principle that specific segments of the neural tube are differentiated along the rostral-caudal axis via expression of specific combinations of Hox genes across their different chromosomal clusters.

28
Q

What specific organization are the Hox genes following in their respective clusters?

A

The distribution of Hox genes in their respective clusters tends to reflect their expression along the rostral-caudal retinoic acid gradient.

29
Q

How are the cell types of the dorsal/ventral regions of the spinal cord generated?

A

By biochemical signals:

Ventral: sonic hedgehog.
Dorsal: dorsalin + BMPs

30
Q

What experiment leads neuroscientists to think that the notochord secretes a factor that induces floorplate formation? Which factor is it?

A

Transplanting the notochord in the mesoderm underlying the ectoderm of the dorsal region leads to floorplate formation in the dorsal region of the neural tube. The factor secreted is Shh.

31
Q

How are ventral motor neurons and interneurons differentiated in the neural tube?

A

They are all differentiated by the Shh gradient of the neural tube floorplate.

32
Q

What can be done experimentally in vitro to show that Shh differentiates progenitor cells of the neural tube?

A

Applying different concentrations of Shh on undifferentiated cells of the neural tube will give rise to different cellular identities.

33
Q

How does Shh signalling work?

A

Shh relieves the inhibition of Patched (PTC, transmembrane protein) on Smoothened (SMO, transmembrane protein). SMO can then activate the translocation of the Gli family to the nucleus.

34
Q

BMPs are also involved in cellular differentiation of the neural tube. What is secreting BMPs? Which region differentiation is induced by BMPs? To which cellular identities are they giving rise?

A

BMPs are secreted by ectodermal cells overlying the neural tube. BMPs induce roofplate formation. BMPs differentiate specialized glia in the roofplate + neural crest cells + dorsal interneurons (sensory).

35
Q

What transcription factor family is activated by BMP signaling?

A

Smad.

36
Q

Which signal of the dorsal region of the neural tube antagonizes Shh’s differentiation of motor neurons?

A

Dorsalin.

37
Q

SUMMARY CARD:

How is the neural fate of ectodermal cells of the gastrula induced?

How is the neural tissue of the most rostral structure of the nervous system (forebrain) induced?

How is the neural tissue of the caudal structure of the nervous system (spinal cord) induced?

How is rostral-caudal axis of the nervous system established?

A

How are the ectodermal cells of the gastrula induced a neural fate?

The dorsal lip of the blastopore (dorsal midline of the mesoderm) secretes neural “inducers” (Noggin, Chordin and Follistatin, etc.). The neural inducers relieve the inhibition of BMP signaling on ectodermal cells, the latter thereby acquiring a neural fate.

How is the neural tissue of the most rostral structure of the nervous system (forebrain) induced?

Neural inducers derived from the organizer.

How is the neural tissue of the caudal structure of the nervous system (spinal cord) induced?

By gradients of FGFs and retinoic acid. Also via the Hox Code.

How is rostral-caudal axis of the nervous system established?

NEUR 310 (12 decks)

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