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Dev Neuro > Semester One 2 > Flashcards

Semester One 2 Flashcards

1
Q

Where is BMP restricted to

A

The area around the neural plate

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2
Q

Closing of the neural tube describe

What’s around the tube

A

F actin causes curving of cells to make the plate into the neural groove

The border cells are what start to curve upwards and together until they meet at the top and fuse.

The roof plate is made of the border cells

Above the neural tube is a layer of non neural ectoderm that used to surround the neural plate

Blow is the notochord and somites

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3
Q

Closing of neural tube TFs

A

1) border cells are expressing BMP. The cell is exposed to medium BMP levels so They then express msx1.

2) Wnts and FGF from the axial mesoderm act with msx1 to turn on a second set of TFs.
Pax3 zic1 pax7. These characterise the border cells.

3) these up regulate other TFs. Cmyc Id and snail. Which govern cell behaviour
4) they will activate genes for proliferation, mulitpotency and survival
5) epithelial to mesenchymal transition allows delamination of neural crest cells from the border region.

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4
Q

Cmyc

Id

Snail

A

Oncogene and over expression means too much proliferation

Gives multi potency

Allows epithelial to mesenchymal transition

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5
Q

Why can mesenchymal cells migrate

A

Epithelial cells are held together by tight junctions

Mesenchymal have the junctions removed so they can delaminate

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6
Q

Neural crest cells

A

Called the fourth germ layer because they give rise to so many cells.

PNS-Schwann, glia, symp and para

Adrenal medulla, melanocytes, facial cartilage and the dentine of teeth and the ENS.

The cell type generated depends on the position of origin of the neural crest cells, the time they were generated and their migratory path and encountered signals.

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7
Q

Three pathways for neural crest cells

A

Migrate to the somites below the neural plate. They are forced into the anterior of the somites by pissofen and become dorsal root ganglia

Migrate below the notochord but above the aorta and form symp and para

Migrate below aorta and become adrenal medulla.

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8
Q

Retained border cells

A

Form the roof plate
Allow the edges of the tube to fuse

Release BMP and Wnts that diffuse ventrally and induce TFs.
Pax 367 and lim1

The cells receiving BMP are already neural and will now react differently. SoxB will be up regulated and they will have a dorsal neural tube progenitor fate.

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9
Q

Roof plate BMP types

A
  • used to be thought that roof plate BMP had one kind and it was like the french flag model.
  • but now we know there are many types of BMP and each type causes a different cell fate and some can diffuse further than others.
  • many different types of progenitors are induced. (cells in mitosis that are not committed)

-distinct neuronal/progenitor subsets
Block 1 closest to the roof plate will become dorsal interneuron 1s. They are induced by a BMP that can’t travel far.

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10
Q

What happens at the same time the neural tube is forming

A

The axial mesoderm forms

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11
Q

How can bilateral symmetry be proven in the neural tube

A

Antibody stains showing the sections.

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12
Q

Graft floor plate and notochord into ectopic location

A

Implanted notochord induces a second ventral floor plate and extra motor neurons.

Normally the notochord will induce the floor plate and a set of bilaterally symmetrical motor neurons.

Shh being secreted from the notochord causes cells to change their identity

The grafted notochord indices host cells.

Hh in drosophila and shh in humans

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13
Q

Shh

A
  • soon after convergent extension shh is up regulated in the notochord
  • a few hours later ssh mRNA is up regulated in floor plate cells.
  • it diffuses in a dorsal direction
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14
Q

How do we know shh is secretory

A

Look at the amino acid structure

Take the mRNA and clone it into an expression vector to see if the protein is secreted from cells.

Make an antibody for shh and watch if it is secreted.

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15
Q

What does shh induce

A

TF expression in progenitors

They will cause ventral neural tube identities

The progenitors will differentiate into ventral neurons.

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16
Q

Soaking a bead in shh and transplanting to an ectopic location

A

A second floor plate and set of ventral neurons are induced.

The notochord is not required. Shh is required.

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17
Q

French flag shh

A

Various concentrations of shh cause different TFs to be up regulated and this will cause the different progenitor subsets.

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18
Q

What determines the type of neuron the progenitor becomes.

A

The amount of shh it was exposed to.

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19
Q

What do neurons closest to the floor plate become

And what do more dorsal ones form.

A

Motor neurons

Sensory relay neurons

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20
Q

What do opposing gradients of BMPs and shh pattern.

A

The DV axis

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21
Q

How do motor neurons and interneurons differentiate finally

A

Extending axons out of the tube into the periphery.

Extend axons in the tube.

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22
Q

Hh signally pathway

Lots of shh means

A

Ptc- 12 transmembrane spanning domains

smo- 7 transmembrane spanning domains

Normally-
Ptc represses smo
Smo can’t activate gli
Gli can’t activate transcription

With hh-
Hh binds to ptc
Ptc can’t repress smo 
Smo activates gli 
Gli activates transcription of hh genes

Lots of shh means lots of transcription

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23
Q

Why is knowing shh concentrations and what they cause important for drug discovery

A

Can make specific neuron types if we know how much shh to use.

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24
Q

Shh knockout

A

No ventralisation of tube

Cyclopia

Abnormal limbs and digits.

Holoprosencephaly-no separation of brain hemispheres

Lack of pituitary and hypothalamus as they are in the centre.

25
Q

What else can induce shh

What does shh determine

A

Prechordal plate

Where seratonergic and dopaminergic neurons are made and the neurons of the hypothalamus

26
Q

Why does the spinal cord get thicker

A

The progenitors are dividing

It starts as a single cell layer neuro epithelium.

27
Q

Radial glia

A

Distinctive shape

Cell body in the ventricular zone

Radial process that extends to the outer neural tube.

The process gets longer as the tube thickens

They are referred to as neural stem cells. They build up the NS throughout embryogenesis

The nucleus shuttles up and down the radial process. Called inter kinetic migration.

28
Q

The neural tube appears to have multiple cell layers but

A

Pseudo stratified and has a single layer.

The cells are proliferating and their nuclei and undergoing inter kinetic migration.

29
Q

Where is the radial glia nucleus in G1 and S phase

In M phase and cytokinesis

A

The nucleus is near the outer peal surface

The nucleus is close to the lumen

At cytokinesis the attachment to the peal surface is lost but reforms after the next G1

30
Q

Early neuroepithelial cells can divide …

A

Symmetrically and give two radial glia which stay in the ventricular zone and are multipotent.

Assymetrically and give a radial glia and a differentiating cell.

The neuron cell uses the radial process of its sister to migrate laterally to the mantle zone

Can be shown on microscope.

31
Q

What determines the type of daughter.

A

Orientation of cell division.
Cytoplasm is on top and membrane determinants are on the bottom.

Horizontal equator split gives two different cells. A radial glia with the determinants and a cell that must differentiate with no determinants.

Vertical meridian split gives two identical radial glia with equal amounts of determinants.

32
Q

Proneural mutant

Neurogenic mutant

A

No cells become neurons because proneural genes are not activated by neuroblasts.

Can’t make notch so more neurons will form than normal. Notch limits amount of neuroblasts produced.

33
Q

What allows a cell to be able to become a neuroblast.

What do they do

A

Exposure to SOG

Only a few cells in the cluster can become neuroblasts and they activate proneural genes and allow neuron production.

34
Q

Notch signalling

Lateral inhibition

A

Lateral inhibition- making identical cells different to one another

1) all cells are equally capable of releasing delta and receiving it with notch.
2) a change or bias causes one cell to be able to make more delta than the others.
3) causing other cells to receive more delta and have more notch activation
4) more notch means more up regulation of suppressor of hairless. And more enhancer of split
5) they repress the production of achaete scute. Which will stop delta production
6) only one of the cells is able to release delta and so it will be the only one not inhibited.

35
Q

Achaete scute

What is Notch involved in

A

Maintains delta production

Bilateral fate decisions

36
Q

What can progenitors produce

And what can these two products produce.

A

Glia or committed neural precursors.

Glia- astrocytes or Oligos

Neural - neurons

37
Q

Sensory neurons can originate from

A

Neural Crest cells and become dorsal root ganglia

Neural tube and become retina.

Placodes

38
Q

Eye field and lens placode

A

Occupies a large part of the ventral neural tube.

Shh is released to cells and causes down regulation of eye field genes.
Splitting the eye field into two bilateral regions.

The eye fields grow out sideways due to proliferation.

They reach the ectoderm and it begins to thicken and becomes the lens placode.

The lens placode will pinch off and form a circle of cells called the lens vesicle.

The eye field becomes the optic vesicle then the optic cup and it becomes the retina.

39
Q

When do the human eyes form

A

3-7 weeks

40
Q

The retina is a specialised out growth of

A

The ventral forebrain.

Diencephalon.

41
Q

Optic groove

A

The optic grooves grow to form the optic vesicles.
Which grown outwards and induce the lens placode on the ectoderm.

Optic vesicles become optic cups.
A single layered neuro epithelium that gives rise to the retina.

The outer cells become retinal pigment epithelium and produce melanin.

The cells in the cup contain a stem like population that can either self renew or differentiate into diverse ganglion cells or interneurons or light sensitive photoreceptors

42
Q

Pax6 ectopic

A

Induce a second retina.

It’s a master eye transcription factor

Conserved through evolution.

Mutations can cause aniridia no iris, small eyes, or no eyes.

43
Q

Retina neuron formation

A

Same way as spinal cord.
Progenitors divide and some differentiate and move laterally.

The longer a cell remains a progenitor the closer it’s position will be to the retina.

There are waves of differentiated cells from five weeks onwards.
The progenitors start in the outer neuroblastic layer close to the retina wall.

Outer layer form rods and cones
Inner layer form bipolar neurons
Inner most layer form ganglion cells.
Each of these are from a wave of differentiated cells.
This is how the laminar structure in the eye is formed.

44
Q

How knowledge can help with macula regeneration

A

Can direct cells to take an optic fate using stem cells.

Sensory neurons in the eye are derived from neural ectoderm and this requires pax6.

45
Q

Most placodes originate from

Except

A

Neural plate border cells in the same way that sensory neurons do.

They give rise to cranial placodes which are specialised areas that form as thickenings on the neural plate border.

Not lens placode.

46
Q

Ear and optic placode

A

Optic placode folds to give a pit and then pinches off to a vesicle

The sensory components come from the neurogenic region in the base of the vesicle.

47
Q

How many neurons in brain

How many connections each

Connections all together

A

10^11

10^3

10^14

48
Q

Two axon connection hypothesise

A

1- Weiss resonance theory 1928
There is random neuronal outgrowth connecting all targets and after there is elimination of non functional targets.

2-Sperry chemoaffinity theory 1939
There is directed and specific outgrowth and axons follow identification tags carried by the cells and fibres of the embryo.

49
Q

Sperry experiment 1963

Then removing both

A

Newts then frogs

Optic nerve was cut and the temporal retina and it’s axons were removed.

Nasal axons grow back along their usual path to the posterior tectum.
They pass the anterior and ignore it.

Meaning each axon has its own path and area to innervate

Removing both the temporal and nasal only left the central retina in tact.
The central axons grew through areas that were not their territory and did not innervate them.
They only innervate their normal areas.

50
Q

Sperry background 3

A

In mammals the tectum is called the superior colliculus

The optic nerve connects the retina to the tectum.

The nasal axons connect the anterior retina to the posterior tectum.
The temporal axons connect the posterior retina to the anterior tectum.

51
Q

Experiment to prove Weiss wrong.

A

If Weiss was right we would see random patterns of axons in the embryo.
However we see that axon outgrowth is organised and stereotyped.

Motor axons are guided specifically to their targets in the Chick embryo.
A section of the neural tube was cut out and replaced but in reverse.
The motor axons could still find their way to their normal muscle targets.
Suggesting axons navigate to their targets.

52
Q

Cajals growth come

A

The growing tip of the axon which can sense cues in the environment

53
Q

Why are axon experiments done on insects.

A

Simple NS

embryos are easy to observe and manipulate

Cells can be a layer using lasers.

54
Q

Axons are cues experiment

A

Axon pathways change when specific axons were encountered.

This was tested by ablating neurons and seeing if axons paths changed.

G turns when it reaches P. But if P is gone G won’t turn.

This is the labelled pathway hypothesis.

55
Q

Labelled pathway hypothesis 5

A

Axons can selectively fasciculate with other axons

Axons surfaces carry cues

Different growth cones express different receptors.

Early axons called pioneers form an axon scaffold on which layer axons can extend.

Eg sub plate neurons in the mammalian cortex. They help direct the LGN neurons to the cortex layer. If part of the sub plate is ablated the LGN innervation fails.

56
Q

Pioneers

And specific growth path

A

They follow paths despite the early environment being seemingly featureless.

T1 pioneer growth cone- makes a turn away at the limb boundary and then another one at cx1.

Ablation of cx1 causes the growth come to stall before it is meant to make its turn.

Cx1 and the limb boundary have no morphological features.

Ablated cells that cause stalling are called stepping stones or guidepost cells.

There must be molecular differences in the environment that cause the axon turning.

57
Q

Axons follow….

A

Boundaries of domains of patterning gene expression.

Boundaries of the floor plate.

Boundaries of rhombomeres.

58
Q

Four forces of axon guidance

A

Contact attraction

Contact repulsion

Chemoattraction

Chemorepulsion

Dev Neuro (7 decks)

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