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building the nervous system Flashcards

1
Q

how many neurons are in the brain and give % of where they are

A

10 to the power of 11, 19% in the cortex, 80% in cerebellum, 1% in the limbic system

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2
Q

what is the urbilateria theory

A

suggests the dorsal vs ventral NS developed as invetabrates due to a body twist
thought that verts and inverts are from a common ancestor there was just a body twist at some point.

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3
Q

how can you set aside tissue of neural identity

A

has to be during/immediately after gastrulation

it is achieved by preventing BMP signalling in ectodermal cells

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4
Q

what does gastrulation result in?

A

in mesoderm and the endoderm being inside and ectoderm being on the outside

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5
Q

what is the organisor?

A

a specialised bit of mesoderm

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6
Q

what does BMP essentially do?

A

keeps the ectoderm as ectoderm that will form skin

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7
Q

what does the organisor do to BMP? why aren’t all cells effected by this?

A

it has BMP antagonist signals, these cells that aren’t stimulated by BMP turn into neural ectoderm.
it cannot diffuse all the way across, only the cells close to the organisor are effected.

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8
Q

what is the neural plate?

A

a single layer of neural cells on ectoderm

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9
Q

what happens if take an animal cap from a pregastrula and grow in isolation? why?

A

form epidermis as there’s no BMP antagonist

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10
Q

what happens if take an animal cap from a gastrula and grow in isolation? why?

A

neural tissue forms and the BMP antagonist is present

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11
Q

what’s under the the ventral part of the neural tube?
what’s under the anterior part of the neural tube?
what’s under the rest of the neural tube?

A

Rod of Axial mesoderm
Prechordal mesoderm
notochord

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12
Q

where must a neural inducer molecule be expressed?

A

in the organiser

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13
Q

what happens if the neural inducer molecule is over expressed in an ectopic site?

A

would lead to the induction of a second axis

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14
Q

what happens if neural inducer activity is inhibited?

A

would prevent axis formation

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15
Q

what is gene redundancy?

A

when there’s back up genes, if something goes wrong with a gene such a mutation then there’s back ups.

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16
Q

how do the Antagonists stop BMP?

A

by either interacting with BMP or BMPR

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17
Q

how does Chordin antagonise BMP?

A

is binds to BMP preventing it from interacting with BMPR

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18
Q

what happens when BMP binds to BMPR? (5)

A

there’s a conformational change
Smad is phosphorylated
smad cannot enter the nucleus activating other genes which leads to SOX being inhibited.
Epidermis is formed

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19
Q

what do antagonist of BMP mean for SOX?

A

sox isn’t repressed
SOX can bind to proneural genes
a neural cell is formed

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20
Q

what is SOX?

A

a transcription factor

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21
Q

what fate does Wnt promote?

A

epidermal

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22
Q

what fate do FGF and FGFR promote?

A

Neural

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23
Q

what’s different about where the invertebrate homologues to BMP and Chordin’s are positioned?

A

they are on the ventral side.

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24
Q

what model is used to explain why you get different neural types along the A/P axis?

A

the activation-transformation model

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25
what happens to the organiser when the neural plate is induced?
it undergoes convergent extension forming a rod of acxial mesoderm/ anterior endoderm
26
what are the three subtypes of cells that make up the organisor after gastrulation?
anterior endoderm, pre-chordal mesoderm, chordamesoderm
27
which cells continue to make BMP antagonists?
the anterior endoderm are the only cells that continue to produce these.
28
how can organiser-derived molecules can induce neural tissue of different A-P types?
because of the activation transformation model
29
how is the anterior (forebrain) tissue induced and maintained?
neural inducing molecules originally come from the early organiser cells but the tissue is maintained only by the pre-chordal tissue once the organisor has differentiated.
30
how is some of this anterior tissue made posterior? why isn't all of it?
because there are other signals that can transform the tissues fate. because posterior signals are antagonised by the prechordal tissue
31
what happens if the anterior isn't maintained? what may cause this?
no head develops, this may be caused by a transcription factor mutating.
32
what does the prechordal mesoderm continue to make?
BMP antagonists
33
what does the anterior endoderm inhibit?
Wnt
34
what happens when Wnt, FGF or RA act on tissue that's going to be anterior? does this happen everywhere?
those cells will change identity and fate and aquire a posterior neural activity. not this doesn't happen in the areas furthest away such as the prechordal and anterior endoderm as these have inhibitors
35
what kind of signals are Wnt, FGF and RA? what does this mean?
morphogens, there's a gradient along the AP axis
36
what are the main posteriorising factors?
Wnts and Retonoic acid
37
does Retonoic acid have receptors?
no because it is so small it can go through the membrane
38
can all genes respond to RA?
no only genes that have the retanoic acid response element
39
what genes do Wnt and RA activate?
SOX and HOX genes
40
what do posterior agents induce?
HOX genes
41
where were HOX genes forst identified?
in the drosophila
42
what do HOx genes do in the drosophila?
specifiy A-P segment identity (provide positional information)
43
what were HOX genes for vertebrates and invertebrates?
the first evidence of homology
44
what does Homeobox DNA encode? what is this?
the homeodomian. this is a DNA-binding protein domain of 60 amino acids
45
what kind of expression patterns do HOX genes have?
nested expression patterns
46
why is each HOX genes slightly different?
they react to slightly different concentrations of RA, the more anterior the lower the conc it responds to
47
how do hox genes determine what the cell will turn into?
the different combination of HOX genes will determine this
48
what happens at the forebrain and hindbrain boundry? what does this secrete? what does this lead to?
a new signalling centre is formed FGF8 and Wnt1 are secreted (morphogens) this is how the midbrain forms.
49
what is neuralation?
neural tube formation
50
what develops at the same time as the neural plate/early neural tube? and where is this?
the notochord, just below the ventral midline of the neural tube
51
if a cell is going to become neural what three things does it have?
Sox genes stem cells progenita cells
52
what happens to the thickness of the neural tube when it forms? what happens to stem cells? what happens to progenita cells?
when it forms it goes from being on ecell thick to numerous cells thick. Stem cells line the lumen however some of these differentiate and when they do they move away from the luminal suface towards the outside of the neural tube. Progenita cells, when they differentiate they move away from the luminal surface to the middle of the layer.
53
what symmetry do neurons develop with?
Bilatteral symmatry around the midline
54
if a system is to be organised with bilateral symettry where must the organisor be placed?
in the centre
55
what are the two ventral organisors and where are they found?
fllor plate cells and notochord. | these are located at the ventral midline.
56
how could it be tested that the organisors secrete organising signals?
by either doing an ectopic graft or by removing the organisor all together
57
in which animal model was the secreted factor discovered? what did mutations in this signal cause?
through work with the drosophila. | mutations caused abnormal development (Hedgehog gene)
58
where is the Shh mRNA expressed?
in the notochord and the floor plate
59
what kind of gene is Shh?
a morphogen, appears in a gradient as it diffuses through the ventral neural tube
60
what happened after Shh soaked beads were implanted on to another embryo
floor plate and ventral neurons were induced to form.
61
what does the ability of a morphogen to change a cells fate depend on?
the concentration of the morphogen, cells closer to the source need higher morphogen concentrations
62
what dictates later differentiation? when does this happen?
the transcription factor code, this occurs as the cells differentiate and move laterally.
63
when does Shh act?
early stage to confer a D-V pattern of transcription factors on progenitor cells.
64
what roles do the transcription factors activated by Shh play?
they are the upstream 'master' regulators of a particular neuronal fate/identity.
65
in the Shh pathway, what happens in absence of Shh?
PTC represses SMO Gli is degraded to it's shorter form this form of Gli enters the nucleus and represses a gene.
66
in the Shh pathway what happens in presence of Shh?
HH binds to PTC this activates SMO Gli the longer for, enters the nucleus the gene is activated.
67
what are PTC, SMO, and Gli?
PTC and SMO are transmembrane domains | Gli is a transcription factor
68
where is Shh expressed?
along the who A-P axis, always ventral.
69
what is caused by multiple dysmorphology in the Shh -/- mouse?
``` no ventralisation of neural tube holoprosencaphaly cyclopedia abnormal lims/digits lack of pituitary ```
70
what does Shh govern?
ventralisation along the entire rostro-caudal axis.
71
what is the neural plate border region?
it's a specialised boundry that gives rise to roof plate cells, these are multipotent and can also become neural crest cells,
72
what gives early patterning first? the roofplate cells or Shh?
roofplate cells
73
what are roofplate cells the source of? what does this cause?
source of morphogens that cause dorsal patterning
74
what is established at the interface of the induced neural plate and surface ectoderm? what does this express? what does this secrete?
an early border expresses specific transcription factors such as MSX secreted signals such as BMPs and Wnts
75
how are progenitor domain established and what are they made up of?
they are established through the opposing morphogen gradients and are made up of proliferating bands of cells.
76
what happens to proginator domains over time? what do they form?
they differentiate and migrate laterally. they form the defined neurons of the spinal cord.
77
where do neural crest cells come from?
from roof plate cells
78
what transition to neural crest cells under go? what does this mean they do?
they undergo the epithelium to mesenchymal transition they can now leave the neural tube epithelium.
79
what do neural crest cells give rise to?
all of the PNS
80
what are neuroblasts?
clusters of cells that have the activated proneural gene, they have the competence to become a neuron however only a few become neurons.
81
what happens in the drosophila proneural mutant?
there are no proneural gened so no neurons form
82
what gene is effected in the drosophila neurogenic mutant and what does this cause?
notch (-/-) | more neurons are formed.
83
what does notch regulate?
lateral inhibition
84
what does lateral inhibition do?
it's a special kind of induction that makes two cells that were initially similar different.
85
how does lateral inhibition work?
initially both cells equally capable of making and recieving the inhibitory signal. a change results in one cell producing more inhibitory signal meaning the other cell recieves more inhibitory signal.

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