Lecture 10 (5a) - Neural Stem Cells in Vertebrates and Invertebrates Flashcards

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1
Q

In Drosophila neuroblasts segregate from the

A

neuroectoderm and the neuroblast progeny are passively dispaced towards interior
• stem cells divide symmetrically to make more (self-renewing)
• asymmetrically –> diff cell fates

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2
Q

The postmitotic neurons migrate

A

out of the ventricular zone and establish the distinct brain layers

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3
Q

Despite the different morphologies, conserved genes

A

are expressed during neurogenesis in vertebrates
• proneural genes
achaete-scute homologues
atonal family
• neurogenic genes - members of the notch signalling pathway

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4
Q

All cells express

A

proneural genes
but notch represses
• determine how many stem cells are formed at 1 time

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5
Q

Neurogenin is expressed

A

in broad stripes in the neural plate of xenopus

• neural plate (outside) folds in and makes neural tube

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6
Q

Notch signalling keeps

A

neural precursor in the epithelium
• Notch keeps neural stem cells pool - ensures symmetric division
• no Notch –> premature divides asymmetrically –> no stem cells
• only fate of newly born neurons (embryonic lethal)

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7
Q

Notch signalling has an additional function in vertebrates

A

Notch signalling is necessary for maintaining the neural stem cell pool

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8
Q

Proneural genes have different/additional functions in vertebrates

A
  • proneural genes promote the generation of neurons but also SUPPRESS THE FORMATION OF GLIAL CELLS (astrocytes) in mammals
  • proneural genes are required for the DELAMINATION and MIGRATION of neurons
  • proneural genes promote CELL CYCLE EXIT
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9
Q

In mammals, proneural genes suppress

A

astroglial differentiation and

promote neural development

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10
Q

Proneural gene function in vertebrates is required for

A

delamination and migration

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11
Q

In contrast to Drosophila, proneural genes promote

A

cell cycle in vertebrates

• Drosophila = no migration

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12
Q

Proneural and neurogenic gene are

A

conserved in vertebrates and invertebrates
• but these genes have partially different/additional functions
(homologs)

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13
Q

Neurogenesis can be subdivided into 4 processes

A
  1. generation of neural stem cells
  2. establishment o neural precursor identity
  3. differentiation of neural precursors
  4. establishment of neuronal networks
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14
Q

2 main processes contribute to the generation of neural diversity (mainly in invertebrates)

A
  • spatial patterning (info from place)

* temporal regulation of formation (timing)

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15
Q

In vertebrates, the identity of a neuron can be influenced

A
  • as it migrates to its final position

* after innervation of its target tissue

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16
Q

Regional identity genes

A

establish neuroblast diversity in Drosophila
• segment polarity for ant/post identity
• stripes in each segment
• remain expressed in neuroectoderm and later specifically in neuroblasts
• longitudinal overlapping –> grid pattern (dorso/ventral)
• each proneural cluster gets positional identity

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17
Q

The expression profiles of the neuroblasts determine

A

the identity o their progeny
• motor and interneurons need even-skipped
• PCC and ACC - longitudinal, motor neurons
• PLACE AFFECTS PROGENY

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18
Q

Gray = neuroblasts express

A

Msh
• no Msh in lateral
(not expressed throughout neurogenesis - only 2 divisions then off)

19
Q

Msh expressed in

A
  • lateral domain of ventral ectoderm in spider
  • continuous lateral domain in the millipede
  • temporal and spatial variations in arthropods
20
Q

The early motor and interneuronal marker eve and islet are expressed in

A

subsets of NPGs in the spider

21
Q

Msh regulates

A

islet expression in the lateral ectoderm
• regional identity genes regulate neuronal sub-type identity similar to Drosophila

  • region determines fate
  • drosophila gene regulation doesn’t transfer to explain it in other organisms
22
Q

Evolutionary changes in the regulation of

A

neuronal sub-type specific genes in arthropods

23
Q

Msh =

A

Msx in vertebrates

24
Q

Temporal identity

The dorso-ventral patterning genes are

A

conserved in vertebrates

25
Q

The number of divisions and type of progeny produced is

A

pre-planned

26
Q

Temporal identity genes establish

A

diversity among the progeny of individual neuroblasts
• color = same neuroblast, delaminates
• divide and change to expression of another gene
• later expression –> dies

27
Q

Temporal identity in Drosophila

A

all segments at the same time

• growth then segmentation in others

28
Q

The expression of temporal genes leads to

A

the formation of distinct neuronal subtypes in neuroblasts 5-6T
• NB 5-6T produces a mixed lineage of 20 cells
• the 4 last born cells are interneurons expressing Apterous (LIM-homeodomain) transcription factor
• the 4 Ap neurons can be further subdivided into 3 different neuronal subtypes

29
Q

Similar to Drosophila, there is a strong link between

A

time of formation and neural identity
• neurons are generated first followed by astrocytes and oligodendrocytes
• ventral motorneurons are born first followed by dorsal interneurons
• the ability of the neural stem cells to produce diverse neural cell types becomes restricted over time
–> Notch signalling and additional factors

30
Q

Neuronal subtype identity genes are expressed in response

A

to the spatial and temporal identity cues

• LIM proteins regulate subtype specificity in motorneurons

31
Q

Summary

A
  • in all bilaterians, neural stem cells are generated in a single layered neuroepithelium
  • proneural genes specify neural stem cells
  • neurogenic genes restrict the number of neural stem cells
  • spatial and temporal identity mechanisms establish the identity of individual neural stem cells and their progeny
32
Q

Euarthropods have a

A

rope/ladder-like axonal
• 2 longitudinal tracts, 2 transversal to connect
• conserved mechanisms = axonal scaffold
• evolutionary modifications = neuronal network

33
Q

Euarthropods show different mechanisms of

A

neural precursor formation

34
Q

Despite differences in the morphology of neural precursor generation

A

conserved genes are expressed
• proneural proteins (members of the Achaete-Scute family) endow cells w/ neural potential
• the members of the Notch signalling pathway restrict the activity of the proneural genes to a subset of cells
• Notch signalling restricts number

35
Q

In insects, proneural genes are expressed in

A

groups of cells PRONEURAL CLUSTERS
D. melanogaster achaete-scute
–> Notch signalling
–> single-spaced neuroblasts (~30)

• neuroblasts don’t segregate
- in perimeter - in neuroblasts

36
Q

The achaete-scute homologues of chelicerates and myriapods are

A

up-regulated in pronerual domains
CsASH, CmASH
–> Notch signalling
–> spaced neural precursor groups (~30 NPGs)

  • achaete-scute homologues are up-regulated in neuroblasts
  • always arrangement of 7 rows of neuroblasts/precursors
37
Q

Daphnia magna ASH is exclusively

A
up-regulated in neuroblasts - proneural clusters are missing
Dam ASH 
Dam asense
neuroblasts are not spaced
(hemi-neuromere)
38
Q

The ancestral pattern of euarthropod neurogenesis

A
neuroblasts
• hexapoda
• crustacea
neural precursor groups
• myriapoda
• chelicerata
single neural precursors
• onychophora
39
Q

Ek ASh is not up-regulated in

A

spatio-temporal domains in the VNE
• ASH upregulated in segregated neural precursors
• low homogenous ASH in VNE

40
Q

Onychophoran neurogenesis doesn’t reflect the state of euarthropod neurogenesis

A
  • proneural genes are up-regulated in proneural clusters/domains or even single neuroblasts (crustaceans) in a regular spatio-temporal patern in ventral neuroectoderm of euarthropods
  • the onychophoran proneural gene is not spatio-temporally regulated in the ventral neuroectoderm
41
Q

Conserved pattern of neuroblasts/neural precursors groups in euarhtropods
(insect, crustacean, millipede, spider)

A
  • about 25-35 neuroblasts/NPGs
  • neuroblasts/NPGs are arranged in 7 row
  • molecular marker gene expression (engrailed)
42
Q

In contrast to euarthropods, a large number of

A

neural precursors segregates in an irregular pattern in onychophorans
• 60-100 neural precursors segregate in each hemi-neuromere

• onychophorans - random precursor arrangement

43
Q

Groups of ectodermal cells are selected in the

A

ventral neuroectoderm of basal insects

44
Q

The ancestral state of neural precursor group selection is

A

maintained in diverse neurogenic regions in insects
• 3 groups of neural precursors invaginate from the stomodeal epithelium and directly differentiate into neurons
• part of the neuroendocrine system of Drosophila derives from neural precursor groups that form in the dorsal midline of the embryonic brain