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Cell Bio & Developmental Genetics > Lecture 7 (3b) The Development of the Nervous System > Flashcards

Lecture 7 (3b) The Development of the Nervous System Flashcards

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1
Q

Overview

A
  1. generation of neural stem cells in a single layer
  2. each stem cell produces a specific part of nerual tissue
    3.identify target cells and form synapses
    form networks
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2
Q

Neurogenesis can be subdivided into 4 processes

A
  1. generation of neural stem cells
  2. establishment of neural stem cell indentity
  3. differentiation of neural precursors
  4. establishment of neuronal networks
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3
Q

The regions that will give rise to the different parts of the embryo are

A

already determined at the blastoderm stage

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4
Q

The neural cells move into the

A

embryo

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5
Q

The ventral nerve cord is

A

simpler than the brain

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6
Q

The ectoderm forms

A

ventral stem cells and makes skin cells

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7
Q

In order to generate all the different cell types of the nervous system, cells go through different stages of development

A
  • competence
  • specification
  • determination
  • differentiation
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8
Q

Neural epithelium goes from a single layer

A

to the neural and skin cells

• have to make competent with specific signals (proneural genes in scattered clusters)

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9
Q

Competence =

A

proneural genes expressed in clusters

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10
Q

Competence

A

all the cells in the neuroectoderm can also become neural cells if they are exposed to the appropriate combination of signals

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11
Q

The appropriate signals that lets the cells in neuroectoderm become neural cells

A

proneural genes

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12
Q

Proneural gens are required for

A

neural stem cell (neuroblast) formation

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13
Q

Proneural genes belong to 2 gene families

A
  • Achaete-scutefamily

* Atonal family

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14
Q

Achaete v Atonal

A
  • achaete - present and expressed

* atonal - more imporant for peripheral nervous system

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15
Q

Proneural proteins are

A

bHLH transcription factors

- bind to DNA

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16
Q

Proneural genes are essential for

A

the formation of the nervous system and sensory organ formation

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17
Q

Pronerual mutant

A

2 of proneural genes is effected

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18
Q

Proneural double mutant

A

double number = barely any nervous system

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19
Q

Sensory organs

A

peripheral nervous system
• flies have sensory bristles with a sensory neuron inside
• proneural mutant = no bristles

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20
Q

Specification

A

cells have received the appropriate signals (expression of proneural genes) to become neural cells
• progression along the neural differentiation pathway can still be repressed by other signals

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21
Q

Cometent cells

A

express proneural genes

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22
Q

Specification

A

only 1 cell of the cluster is turned into neural stem cells by neurogenic genes
• some become skin cells (binary decision pathway)
• neurogenic genes see that enough cells left for epidermis
–difficult to restrict to 1 cell to neural stem cell

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23
Q

The antagonistic signal

A

neurogenic genes restrict proneural gene expression to a single cell
• proneural genes - essesntial for neuroblast formation
• neurogenic genes - restrict the number of neuroblasts
–decision bettween between epidermal and neural fate

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24
Q

Mutant neurogenic gene

A

the whole cluster of neural stem cells

  • -> embryos die at embryogenesis
    • lots of nervous no skin in periphery = more sensory bristles
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25
The neurogenic genes that are transmembrane proteins
Notch and Delta • intra, trans, and extra cellular receptors • communicate so notch receptor and delta ligand come together • don't diffuse far so must be neighboring = cluster
26
There is only 1 neuroblast in a cluster of
epidermoblasts | • differ in amount of proneural
27
Model for interaction of proneural and neurogenic genes
only 1 neuroblast in a cluster of epidermoblast • differ in amount of proneural • transcription factors switch on Delta ligands and binds to Notch recpetors on neighbor --> neighbor not able to make neuroblast • enhancers esp with negative effect on Delta = FEEDBACK LOOP
28
Notch signalling inactive
proneural gene expression high | --neuroblast
29
Notch signalling active
proneural gene expression low | -- epidermoblast
30
Determination
* no longer responds to Notch signalling | * neuroblasts in fixed positions in neural ectoderm (ventral)
31
Differentiatin definiton
cells have entered the neural differentiation pathway and will become neural cells even int he presence of inhibitory signals (neurogenic genes)
32
Neuroblasts delaminate from the neuroectoderm region their
determination
33
Neuroblasts produce
ganglion mother cells (GMC) | • self renew because uneven division
34
Asymmetric cell division =
asymmetric division of neural cell fate determinants • basal complex - inside • apical complex - outside
35
Par is in all
asymmetric | • organize asymmetric division
36
Neural cell fate determinants are localized to the
ganglion mother cell • Miranda = protein binding protein • mitotic spindle rotates • 1 cell gets all neural cells, 1 protects
37
Divide asymmetrical -->
1 can become another kind of neural cell
38
Neural stem cells only give rise to
cells of the neural system
39
Early born neurons form the
deepest layers of the central nervous system
40
Neural stem cells
* self-renewing capacity * asymmetric cell division * pluripotent (capable of giving rise to many different cell types)
41
In all bilaterians the neural progenitors of the central nervous system arise from
a single-layered neuroectoderm • dorsal neural plate --> neural cells only (no epiderm) (drosophila has a ventral nervous system)
42
Neurulation
the neural plate folds into a tube | • in contrast to Drosophila, all cells become neural cells in vertebrates
43
Different types of neural stem cells are generated in the
neuroectoderm neuroepithelium = aka = neuroepithelium • tube-like structure inside --> nervous system
44
Radial glial cells
long, thin processes • different layers of the brain -- are actually stem cells - give rise to neurons • radial and glial attached to basal and apical • basal - not attached to apical
45
Neuroepithial and radial glial cells divide at the
apical surface | • interkinetic movements of the nuclei
46
Multiple layers
* brain multi-layered | * spinal cord is not multi-layered
47
Asymmetric division -->
neural epithelium looks multi-layered bc nuclei move up and down - in the spinal cord (everywhere but brain) (symmetrical --> more stem cells, post mitotic neurons)
48
The post mitotic neurons migrate out of the
ventriclar zone | and establish the distinct brain layers
49
The brain has
layers • active migrations if neurons to deeper --> layers of the brain
50
Despite the different morphologies, conserved genes are expressed during
neurogenesis in vertebrates • proneural genes: eg achaete-scute homologues, members of the Atonal family (Atonal genes, neurogenins) • neuronic genes: members of the Notch signalling pathway
51
Proneual genes
* achaete-scute homologues | * members of the Atonal family (Atonal genes, neurogenins)
52
Neurogenic genes
members of the Notch signalling pathway
53
Members of the Atonal family only after
establishment of neural stem cells
54
Neurogenin is expressed in
broad stripes in the neural plate of Xenopus | • Neurogenin is in more cells than NeuroD
55
Notch signalling keeps
neural precursors in the epithelium
56
The neural plate is all
neural cells • Notch keeps some cells from becoming neural stem cells • not the case in vertebrates - need ordered production of neurons bc fate of neurons depends on the time formed
57
Notch signalling has an additional function in vertebrates
Notch signalling is necessary for maintaining the neural stem cell pool • Notch restricts the number of neural stem cells that make neurons
58
Proneural genes have different/additional functions in vertebrates/mammals
* proneural genes promote the generation of neurons * also suppresses the formation of glial cells (astrocytes) in mammals * required for the delamination and migration of neurons * promote cell cycle exit
59
In mammals proneural genes
suppress astroglial differentiation and promote neural development
60
Proneural gene function is required for
delamination and migration
61
In conrast to Drosophila, proneural genes promote
cell cycle exit in vertebrates
62
Proneural and neurogenic genes are conserved in vertebrates and invertebrates, but these genes have
partially different/additional functions
63
2 main processes contribute to the generation of neural diversity
* spatial patterning | * temporal regulation of formation
64
In vertebrates - in some cases the identity of a neuron can be influenced
a) as it migrates to its final position | b) after innervation of its target tissue
65
Regional subdivision of ventral neuroctoderm
A D V P makes a grid of MR IR LR
66
Each neuroblast expresses a different subset of
segment polarity and dorso-ventral patterning genes
67
The dorso-ventral patterning genes are
conserved in vertebrates
68
Temporal identity genes establish
diversity among the progeny of individual neuroblasts
69
Similar to drosophila, there is a strong link between
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
70
Neurons are generated first followed by
astrocytes and oligodendrocytes
71
Ventral motorneurons are born first followed by
dorsal interneurons
72
The ability of the neural stem cells to produce diverse neural cell types
becomes restricted over time
73
Neuronal subtype identity genes are expressed
in response to the spatial and temporal identity cues
74
In all bilaterians, neural stem cells are generated
in a single layered neuroepithelium
75
Proneural genes specify
neural stem cells
76
Neurogenic genes restrict the number of
neural stem cells
77
Spatial and temporal identity mechanisms establish the identity of
individual neural stem cells and their progeny

Cell Bio & Developmental Genetics (27 decks)

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