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NSCI 200 - Intro to Neuroscience 1 > Lecture 16 - Early Brain Development II > Flashcards

Lecture 16 - Early Brain Development II Flashcards

1
Q

Where is fibroblast growth factor 8 (FGF-8) found?

A

FGF-8 is concentrated at the isthmic constriction (junction between the mesencephalon and rhombencephalon).

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2
Q

What does FGF-8 do?

A

FGF-8 induces expression of the Engrailed transcription factor in gradients that decrease anteriorly and posteriorly from the isthmus, thus defining this region.

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3
Q

What does a FGF-8 soaked bead implanted into the diencephalon do?

A

It mimics polarizing activity of the isthmus, inducing Engrailed and transforming the diencephalon into midbrain.

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4
Q

In what organism were Hox genes originally identified?

A

Drosophila

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5
Q

True or False?:

Drosophila larvae and adults have pronounced segmentation in their body.

A

True

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6
Q

How does segmentation affect gene expression in Drosophila larvae?

A

Various different genes are expressed in different sements in the Drosophila. Expression is isolated in specific segments to give rise to a specific body plan.

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7
Q

What is the Drosophila Hox gene cluster?

A

The hox gene cluster is a cluster of genes for many different proteins on one chromosome. Different genes from the Hox cluster are expressed in different segments in the Drosophila. The order these genes are expressed on the chromosome is the same as the order in which they appear in the body plan.

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8
Q

What happens in a Drosophila homeotic (Hox) mutant deficient in Ubx?

A

The appendage on segment T3 on Drosophila is normally a haltere (a small balancing organ). A mutant deficient in Ubx expression grows a second pair of wings instead of a haltere.

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9
Q

What is the structure of Hox genes in humans?

A

Hox genes in humans are composed of 39 genes in 4 clusters on 4 differnet chromosomes in humans.

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10
Q

Where are human Hox genes especially essential for regionalization?

A

Hindbrain

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11
Q

What are rhombomeres?

A

Rhombomeres are repeating units in the neural tube within the forming rhombencephalon. They are semi-isolated compartments of gene expression, cell mobility, and adhesion. They help define cranial nerve nuclei and contribute to their development.

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12
Q

Bell et al. performed an experiment in which they transplanted part of one rhombomere into a region in which it normally shouldn’t be in a chick embryo. What happened? What does this tell us?

A

The transplanted region formed a nerve into the original ganglion it was meant to innervate. This tell us that the genes the rhombomere expresses decide what kind of nerves it forms.

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13
Q

True or False?:

Wnt antagonists have a gradient that decreases from the spinal cord towards the midbrain (posterior to anterior) while Wnt, RA, Fgf, and TGFβ have a gradient that decreases from the forebrain towards the hindbrain (anterior to posterior).

A

False

Wnt, RA, Fgf, and TGFβ have a gradient that decreases from the spinal cord towards the midbrain (posterior to anterior) while Wnt antagonists have a gradient that decreases from the forebrain towards the hindbrain (anterior to posterior).

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14
Q

What gives rise to differentiation in anterior-posterior embryo development?

A

This development is caused by a concerted activity of signaling proteins and transcription factors.

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15
Q

How do we create diverse neuronal and glial cell types?

A

Cells undergo cell specification events to differentiate them into a specific neuronal or glial cell type.

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16
Q

What is the difference between regionalization events and specification events?

A

Regionalization events produce regional specializations to give neural progenitors a positional identity and an associated developmental potential. Specification events help determine cell type (moto neuron vs interneuron, neuron vs glial cell, etc.).

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17
Q

True or False?:

The dorsal-ventral axis is important for establishing the fate or neural cells. It is regulated by signals from non-neural cells.

A

True

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18
Q

What are two important signals in the spinal cord that act along the dorsal-ventral axis? Where do they act from?

A

Sonic Hedgehog (Shh) - Acts ventrally from the notochord and floor plate.

BMP - Acts dorsally from the ectoderm and roof plate.

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19
Q

What do Shh and BMP in dorsal-ventral axis signalling do?

A

They turn on genetic programs that help specify cell fate.

20
Q

What is marked in the image below of the chick spinal cord?

A

Sonic Hedgehog

21
Q

True or False?:

Shh is necessary for specification of ventral cell types. It requires coordination with other secreted proteins for this specification to occur.

A

Shh is both necessary and sufficient for specification of ventral cell types.

22
Q

How does Shh cause the transcription of specific genes?

A

Under normal circumstances, the Shh receptor Patched inhibits Smoothened, an activator for transcription factor Gli1. When Shh binds to Patched, Smoothened becomes uninhibited and can go on to signal to Gli1, which causes the transcription of specific genes.

23
Q

What would happen during development if a second notochord were transplanted?

A

You induce the formation of floorplate and neurons where they would not typically be formed.

24
Q

What would happen during development if the notochord was ablated (removed)?

A

There would be no Shh signal and none of the cells above it would specialize into their correct type.

25
Q

True or False?:

A complete mix of transcriptional activation/repression events regulate gene expression of ventral and dorsal cell types.

A

True

26
Q

What happens in mice when the gene encoding the transcription factor Lmx1a is spontaneously mutated? (BMPs promote expression of Lmx1a.)

A

This mutation causes a reduction in dorsal brain structures.

27
Q

What three processes allow our brain to grow and develop?

A

Proliferation, Differentiation, and Migration

28
Q

What happens during the 4 stages of the cell cycle for neural precursor cells within the ventricular zone?

A
29
Q

What are neuroblasts? What are glioblasts? What do they come from?

A

Neuroblasts are lineage restricted progenitor cells that will go on to become neurons. Glioblasts are lineage restricted progenitor cells that will go on to become glia. They both come from progenitor cells, which come from stem cells.

30
Q

What is the difference between stem cells and progenitor cells?

A

Stem cells are self-renewing, pluripotent (can give rise to any cells in the body), and slow-dividing. Progenitor cells have limited self-renewal capabilities, are multi- or uni-potent, and fast dividing.

31
Q

What are the 6 steps in the molecular and cellular mechanism that guides neuronal and glial differentiation?

A
  1. Neural Induction
  2. Organizer Centers
  3. Neural Patterning
  4. Neurogenesis
  5. Oligodendrogenesis
  6. Astrogliogenesis
32
Q

What facilitates the specialization of ectoderm into neuroectoderm during neural induction?

A

Noggin/Chordin

33
Q

True or False?:

Neurogenesis, oligodendrogenesis, and astrogliogenesis are all time-dependent differentiation events.

A

True

34
Q

In which two regions of the brain are new neurons formed?

A

Olfactory Bulb and Subventricular Zone (SVZ)

35
Q

What discovery did Yamanaka and Gurdon win the 2012 Nobel Prize in Physiology or Medicine for? What experiments did they perform to prove this? What is the importance of this discovery?

A

They won it for the discovery that mature cells can be reprogrammed to become pluripotent.

Gurdon eliminated the nucleus of a frog egg cell and replaced it with the nucleus from a specialized cell taken from a tadpole. The modified egg developed into a normal tadpole. Subsequent nuclear transfer experiments have generated cloned mammals.

Yamanaka studied genes that are important for stem cell function. When he transferred four such genes into cells taken from the skin, they were reprogrammed into pluripotent stem cells that could develop into all cell types of an adult mouse. He named these cells induced pluripotent stem (iPS) cells.

iPS cells can now be generated from humans, including patients with disease. Mature cells including nerve, heart, and liver cells can be derived from these iPS cells, thereby allowing scientists to study disease mechanisms in new ways.

36
Q

Why is neural crest cell migration referred to as “free migration”?

A

It is called “free migration” because it occurs without radial glia scaffolding.

37
Q

Which types of neurons is long-range migration especially important for?

A

Cortical GABAergic Interneurons and Oligodendrocytes

38
Q

True or False?:

In lamination of the cerebral cortex, the young neurons form new layers underneath the existing layers of older neurons, pushing those layers further away from the ventricular zone.

A

False

New neurons migrate past existing layers of older neurons, forming new layers further away from the ventricular zone.

39
Q

At the end of cerebral cortex lamination, how many layers are there?

A

6

40
Q

What is used for radial migration in the developing cortex?

A

Radial Glia

41
Q

What is lissencephaly?

A

Lissencephaly (meaning “smooth brain”) is a set of over 25 rare brain disorders where the whole or parts of the surface of the brain appear smooth. Children with it may appear normal at birth but often show intellectual disability and seizures during the first year.

42
Q

What is the difference between normal and lissencephalic cortex laminar patters? What causes this?

A

Lissencephalic laminar patterns do not have layers like normal laminar patters. This indicates the disease is caused by genes that interfere with migration.

43
Q

What is reelin? What does it do?

A

Reelin is a protein that is secreted at the top of the cortex by the radial glia (glial endfoot). It is thought to be a signal to tell migrating cells to stop migrating and remove themselves from the radial glia.

44
Q

What happens in Reeler mutant mice that don’t contain reelin?

A

The absence of reelin causes cells to disattach from the radial glia at varying points, causing the cortext to be disorganized instead of being organized into distinct layers like they are in a normal cortex.

45
Q

What are the three types of migration during brain development?

A
  • Neural Crest Migration
  • Long-Range Migration
  • Local Migration

NSCI 200 - Intro to Neuroscience 1 (23 decks)

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