Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Mechanism Of Brain Development > Prof Andrew Jarman > Flashcards

Prof Andrew Jarman Flashcards

You may prefer our related Brainscape-certified flashcards:
The Brain flashcards
1
Q

What is the name of the binding accessory which stabilise the array of microtubules in an axon? Name this binding accessory that is specific to dendrites and axons.

A

Microtubule-associated protein (MAP) and Tau

Dendrites: MAP2

Axon: MAP1B and Tau

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

State the mechanism in which axon elongates

A

Elongation occurs not by stretching because the microtubules are rigid, instead they laid out new membrane components to elongate themselves.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

In the Ena/VASP mutation, what was the observation? And which structure is affected?

A

The mutant cannot formed lamellipodia and does not seem to exhibit actin dynamics. ENA/VASP protein are known to be involved in actin polymerization and chemotaxis of the lamellipodia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe the six stages of neurite outgrowth

A
  1. Neural precursor cells is spherical. The mesh-work of actin filaments under its plasma membrane act as a barrier and prevent the formation of outgrowth.
  2. Actin filament is disrupted at specific points -> allows penetration of microtubules -> formation of lamellipodia and filopodia
  3. The initial sprouts are very dynamic -> initial sprouts is formed but is still very much dynamic
  4. Cells becomes polarised: one become the dendrites and one become the axon
  5. Remaining neurites stopped their cycles of being ‘dynamic’ and develop into branches or mature into dendrites.
  6. Neutrons established their identity by its morphology (some develop dendritic spines)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What protein in laminin? Which process does it involves in?

What is CSPG?

A

Laminin is a complex protein with multiple domains that binds to other proteins in the ECM and on cells and axons. It is a potent inducer of neurite outgrowth.

CSPG inhibit laminin-induced outgrowth of cultured cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Name two mechanisms which is required for the formation of filopodia and lamellipodia. And how do they able to achieve this?

A

Cytoskeleton rearrangements and recruitment of new membrane components to the growing site. Through complex network of signalling molecules and second messengers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the name of the two factors that could switch between the inactive and active state of small G proteins?

A

GEF - guanine nucleotide exchange factor, swap bound GDP to GTP causing activation

GAP - GTPase activating protein, promote G-protein catalysed hydrolysis thereby causing inactivation of G protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

List the members of the Ras superfamily and what do each members of the family regulate?

A

Rho, Rac and Cdc42

This superfamily is involved in cell shape regulation, activating gene expression and promote neural survival and plasticity.

Rho: inhibit axon elongation
Rac: promotes axon elongation
Cdc42: initial outgrowth and neurite branching

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what set up the pattern of gene expression?

A

morphogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the 15 segmental units in the insect nervous system?

A

ganglia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

which comes first? diversification or segmentation of neurones?

A

diversification

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

at the syncytial blastoderm stage, are the cells identical to each other?

A

cells look morphologically identical but they are already expressing different genes. EVEN BEFORE GASTRULATION AND NEURAL INDUCTION OCCUR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what does the French flag model demonstrate?

A

it demonstrate that molecules respond to different morphogen concentrations and the response is activation of inhibition of gene expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

which axis does the bicoid and hunchback diffuse through?

A

anterior to posterior

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what do bicoid and hunchback activate and how to they do it? what do you refer to this molecule which can induce gene activation in a certain manner?

A

gap genes in threshold dependent manner

morphogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

where in the embryo does hb regulate the expression of kr?

A

in the middle of the embryo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

how does the expression of gap genes later established a distinct and sharp domain?

A

example: kruppel and giant

kr and gt have repressive interactions this helps to sharpen their expression boundaries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what do gap genes encode?

A

zinc finger TF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how is the AP identity of cells established?

A

through the combination of gap and pair-rule genes which activates hox genes in different AP domains.

therefore different segments express different combinations of hox genes -> identity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what do the hox genes encode? and how do these genes arose?

A

the encode homeodomain TF

tandem duplication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is the homeotic effect?

A

mutation which causes one body part to resemble another (Ubx mutant has additional wings in different segment)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

which structure has segments called rhombomeres?

A

hindbrain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

we know in drosophila hox genes are important in patterning the AP axis, what about in vertebrates?

how is the what hox genes regulate differ in both drosophila and vertebrates?

A

pattern this hindbrain and SC

e.g. rhobomeres (segments)

in drosophila the mutations are simpler but in vertebrates mutations of different regions in rhombomeres causes more complex phenotype hence, hox genes also plays a role in segmentation in addition to segment identity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what are the fours early graded signals which regulates the hox genes? which ones are the posterirorizing signals?

A
  • BMP
  • Wnt
  • FGF
  • Retinoic acid

last three are posteriorizing signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

name the signal which sets a default anterior fate of the neural plate

A

BMP inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

later graded signals are posteriorising signals how do the neural plate maintain its anterior identity?

A

through a third signal (extreme anterior) called cerberus (Wnt/FGF inhibitors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is retinoid acid? how does RA regulate the expression of Hox genes?

A

RA is a small organic molecule related to vitamin A

it crosses the membrane of the recipient cell where it forms a complex with RA receptor (RAR).

the RA-RAR complex translocates into the nucleus where it target genes by binding to DNA sequence called retinoid acid response element (RARE). Thus regulate the expression of some hox genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

is hox genes expressed in the anterior brain?

A

NUUUUUU. anterior brain referring to forebrain/midbrain. but they are expressed in the hindbrain -> SC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

name the six genes which gives each segment of the brain its identity and pair them with the ones they formed boundaries with

A

Six3 -> Irx3

Pax6 -> En1

Otx2 -> Gbx2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

where do neuroblasts gain their identity from?

A

from their location

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what gave rise to two new signals being produces in the AP of each segment in Drosophila? what happened after this?

A

interactions of TF between the AP cells give rise to expression of wg and hh mRNA.

the mRNA translates into protein which creates a local gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what gives neuroblasts its unique individual identity?

A

intersections expression of genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

how do new signalling centres formed?

A

they formed at boundaries between gene expression for local patterning

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

where is the isthmic organiser located and what does it expressed?

what structure develop and a result of this patterning?

A

boundary between midbrain and hindbrain

FGF8 and Wnt1 which diffuses locally through the midbrain (FGF8). in which it activates TF encoded by en1 and en2 -> formation of the cerebellum and tectum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

remember the irx3, six3, etc are genes that creates and set BOUNDARIES and THEY ARE TF GENESSSSS

A

Otay.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

what are the three features of morphogen (in terms of how they affect the cells)?

A
  1. they formed a concentration gradient
  2. induce activation or inhibition of gene expression in cells that respond to it
  3. they provide positional information
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

what is homeotic transformation? give an example and what do they conclude when the observed mutation in the Hox gene causes homeotic transformations in segment identity?

A

homeotic transformation is when the mutation of a hox gene causes the mutated segment to resembled the identity of another segment.

mutation in Ubx (ultrabithorax) gene causes the third segment to develop as if it has the identity of the second thoracic segment.

therefore the normal function of Hox gene is t assigned identity to a segment, selector genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

what do columnar genes encode?

A

homeodomain transcription factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

where do neuroblasts gain their identity from?

A

from their location (remember the interesting expression of AP and DV TF)

40
Q

what are the two signals being produced that is responsible in local AP patterning in drosophila and how does this occurred?

A

WG: wingless
HH: hedgehog

interactions between A and P cells lead to these two new signals being produced and formed a diffusible gradient

41
Q

what are the two signal proteins with opposing activity that formed a morphogen gradients important in patterning the AP axis in DROSOPHILA?

A

dorsal: DPP
ventral: dorsal, a TF for ventral pattern

42
Q

which type of gene does dorsal and DPP activate?

A

they both activate the columnar genes in drosophila. the columnar genes respond to different levels of DPP and dorsal

43
Q

therefore segmentation genes gives neuroblasts their ….(1) location and columnar genes give neuroblasts ….(2) location in Drosophila

A
  1. AP

2. DV

44
Q

in the neuronal patterning in VERTEBRATE NEURAL TUBE, where does the signal come from that is responsible for local AP patterning and DV patterning?

A

AP patterning: signal comes from interaction at boundaries between rhombomeres and anterior brain region

45
Q

in vertebrates neural tube, what is the name of the group of cells which forms signalling centre at the boundary between midbrain and hindbrain? what genes does this signalling cells induced and what does it form?

A

isthmic organiser

induces the expression of gene En1/En2 which code for TF

En1 -> midbrain -> tectum
En2 -> hindbrain -> cerebellum

46
Q

which cells in the neural plate becomes the neural crest cells?

A

lateral cells of the neural plate

47
Q

in vertebrates neural tube what give rise to distinct type of neurones?

A

the progenitor domains established at different DV levels

48
Q

which part (layer) of the embryo is important for neural induction? why is this so?

A

underlying mesoderm

signalling from the underlying notochord is important in patterning the neural tube

49
Q

what is the ventral signal from the notochord that is important in defining the identity of the ventral midline?

A

notochord which produces SHH

50
Q

describe the hedgehog signalling pathway

A
  1. receptor of HH, patched inhibit smoothened
  2. when HH binds, patched is downregulated and smoothened no longer inhibited
  3. smoothened translocate to the membrane surface where it inhibits the cleaving of GLI (smoothened is a GLI activator)
  4. GLI translocate to the nucleus where it exert an effect of modulating gene expression by binding to the double helix.
51
Q

in vertebrates neural tube, which induces the floor plate and which induces the roof plate?

A

floor: SHH by the underlying notochord
roof: induced by BMP

52
Q

low[SHH] induces which type of neuronal fate?
medium[SHH] ..
high[SHH] ..

A

low: Vo and V1
mid: V2
high: MN and V3

53
Q

SHH is important in DV patterning in

A

vertebrates only.

54
Q

what is the type of gene does SHH induce in neural tube? how does the progenitor domain determined from this?

A

it induces homeodomain TF

combination of gene expressed in each domain is a homeodomain code for the progenitor domain

55
Q

what gives rise to the different identities of motor neurone in the AP axis?

what give rise to the formation of motor neurones ventrally throughout the neural tube?

A
  1. Hox genes

2. Nkx genes

56
Q

what controls neural subtype determination?

A

spatial and temporal mechanisms

57
Q

what are the three aspects that differ axons and dendrites?

A

morphology, function and molecular structure

58
Q

does microtubule have polarity?

A

yes

59
Q

subunit of actin filaments
subunit of microtubules

what happened to the dynamic of these cytoskeleton in mature neuritis?

A

actin subunits
alpha/beta subunits

they are stabilised

60
Q

what are the aspects that differ dendrites from axons?

A

microtubules in dendrites are not so well aligned

have different MAPs which can be use as a marker to differentiate dendrites and axons

61
Q

describe how axons grow

A
  1. they are rigid structure therefore extension occurs by addition of new cellular components instead of stretching out
  2. the building block for the membrane addition is transported from the cell body into the growth cone
62
Q

what happens when the growth cone senses favourable growth cues?

A
  1. actin will capture one of the microtubules extensions (microtubule capture)
  2. actin filament that captures the microtubule would extend hence pushing the microtubule towards the direction of the cue
63
Q

what happened during acquisition of polarity in immature neurites?

A

an axon emerges and the rest produce branches and spines - dendrites

64
Q

name the extracellular signals that influence outgrowth:

  1. diffusible signals
  2. ECM
A
  1. Wnt, growth factors (e.g. neurotrophic), SHH

2. laminin, proteoglycans and collagen, etc

65
Q

what was observed when rat neural crest cell line was grown on laminin and laminin and CSPG-coated surface?

A

laminin: differentiate into neurones with outgrowth forming

CSPG-laminin: cannot form axon outgrowth

66
Q

how do signals influence outgrowth?

A
  1. bind to receptors on the surface of growth cone which triggers intracellular signal transduction
  2. leads to cellular responses such as changes in cytoskeleton structure and dynamics
67
Q

explain the ENA/VASP mutant phenotype.

A

ENA/VASP required for actin dynamics (formation of filopodia and lamellipodia) -> disruption of dynamics -> cannot grow filopodia

68
Q

what is the underlying principle which induces the expression of specific proneural genes in the development of vertebrates CNS?

A

BMP and SHH induces the expression of homeodomain TFs across the DV axis.

the overlapping expression of these transcription factors (e.g. Pax7, Nkx6.1, Nkx2.2) create unique combinations which define different progenitor DOMAINS

and in turn, this induces the expression of proneural genes such as Atoh1, Ascl1 and Neurog1

69
Q

explain briefly what is lateral inhibition

A

it is a mechanism to ensure only one neural cells from the proneural clusters takes the step from competence to commitment

this involves the Notch signalling pathway

70
Q

what is the role of Atoh1 gene?

A

make cells competent to become a particular cell types e.g. sensory hair cells in Drosophila

71
Q

which gene expression is UPREGULATED in committed cells?

A

proneural gene expression

72
Q

which type of division does radial glial cell undergoes?

A

asymmetric division to produce different neural subtypes

73
Q

which bHLH + HD factors activate Ascl1 and Neurog1?

A

Ascl1: Pax7

Neurog1: Pax6 + Nkx6.1

74
Q

radial glia in the pMN produces

A

a mixture of neurons and glia

75
Q

in the pMN progenitor domain:
first born cells differentiate as …(1)
later born cells differentiate as …(2)

A
  1. motor neurons

2. glial cells

76
Q

what happened when a single isolated progenitor cell is cultured in vivo? what does this mean?

A

they produce several different neural cell types, therefore they are multipotent stem cells

77
Q

apart from unique combination of patterning and proneural factors what else affect neural subtype differentiation?

A

birth date

78
Q

name a mechanism in which neurons in the drosophila embryo can be arranged spatially and name which structure in the human adopted similar mechanism

A

arrange according to their birth date

formation of the cerebral cortex layers (laminae)

79
Q

what is the mechanism adopted by the ganglion mother cell to produce different neuron cells over time?

A

by expressing different TF at different times.

80
Q

describe how the cortical laminae are formed

A

they are formed in an inside-out manner overtime

  1. cells are born from the subventricular zone - the deepest layer
  2. early born cells innervate the deeper layers first
  3. later born cells migrate to innervate the superficial plial surface

remember the progenitor cells are also radial glial cells

81
Q

what does proneural genes trigger?

A

NEURAL DIFFERENTIATION

82
Q

what is heterochronic transplant?

A

transplantation of old neural stem cells to young niche

83
Q

what does svp regulate in drosophila? its vertebrate homologue in mouse retina

A

svp regulate Hb involved in differentiation of mother ganglion cell

svp homologue is coup-tfl

84
Q

describe how small g proteins Rac act as a molecular switch

A
  1. when positive signal is received from the growth cone, receptor activation lead to activation of guanine nucleotide exchange factor (GEF)
  2. GEF displaces GDP initially attach to Rac to GTP which results in activation of Rac
  3. Rac-GTP binds to other proteins that modulate cytoskeletal stability
  4. some receptor activation leads to the switching back of Rac to its inactive state
  5. this is done by activation of GTPase activating protein which dephorphorylate GTP to GDP, inactivating Rac
85
Q

in control of cytoskeleton dynamics,

+ve signal activates .. (1a), responsible in ..,(1b)
-ve signal activated ..(2a) and ..(2b)

Rac and Rho ..(3) one another

growth factor activates ..(4)

A

1a. Rac - 1b. axon elongation
2a. Rho
2b. CDC42
3. inhibits
4. Ras

86
Q

what is the name of the signalling molecule activated by Ras? what does it involve in?

what does cdc42 involve in?

A

PIP3, elongation

cdc42 -> initial outgrowth (of filopodia and lamellipodia) and branching

87
Q

what molecule does small g protein regulate? name them and their effects

A

regulate effector proteins which remodel cytoskeleton

  1. Arp2/3 complex - promote nucleation of new actin filament hence branching
  2. cofilin - promotes severing of actin filaments creating more barbed ends for EXTENSION
88
Q

which signalling pathway is required for neuronal polarity? and describe this pathway

A

PIP3 signalling pathway

  1. growth factor activates small g protein Ras which activates the enzyme PI3K.
  2. PI3K phosphorylates second messenger membrane-bound PIP2 to PIP3.
  3. PIP3 activates Akt and inhibits GSK-3beta which promotes microtubule stabilisation
89
Q

which artificial microtubule stabilisation can trigger axon specification?

A

taxol and laminin

90
Q

name the extracellular signals present in vivo which triggers axon specification

A

neurotrophin 3 which activates PIP3 -> microtubule stabilisation

91
Q

name the possible mechanism which causes the formation of only one axon

A

microtubule stabilisation lead to enhance transport of more PIP3 into the particular neurite -> rapid elongation of neurite as axon -> other neurites straved of PIP3 form the cell body

92
Q

name the MAPs present in axon and dendrites

A

axon: MAP1B and Tau
dendrites: MAP2

93
Q

name the small g proteins involved in the outgrowth of dendrites

A

rho, rac and cdc42 (particularly required for dendrite branching)

94
Q

describe the mechanism by which dendrites branches

A

interstitial branching - formed along the dendrites

  1. local activation of cdc42 lead to penetration of actin gel at dendrite surface
  2. formation of transient filopodium
  3. filopodium invaded by microtubules and stabilised as a new branch
95
Q

name the purpose of dendrites that do not overlap each other when originating from the same cell body

A

ensures that neuron samples its receptive field evenly

96
Q

name a molecules important in self-avoidance of dendrite branches in drosophila and vertebrates which structure of the dendrites plays part in this recognition of different CAMS?

A

drosophila - DSCAM
vertebrates - protocadherins

the growth cone

Mechanism Of Brain Development (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions