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Neurodevelopment Summary

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Vak
Neurodevelopment (NWIBB039C)

Instelling
Radboud Universiteit Nijmegen (RU)

Boek
Development of the Nervous System

This summary contains the theory from the book, the lectures as well as the experiments shown to proof the theory. The theory and experiments are presented in a informative but understandable matter. I've got a 7 by just learning this!!

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Neurodevelopment

H1- Neural induction
The ectoderm gives rise to skin and the central nervous system (CNS).

During gastrulation formation of the three germ layers, ectoderm, mesoderm, and endoderm takes
place so that the cells can undergo induction.

AB blastomeres give rise to skin as well as neurons. Neurons primarily derive from hypodermis and
move inside (Migration to the interior side).

1. Invagination of the ventral furrow (mesoderm) takes place
2. Gastrulation: Mesoderm is in the interior side and the neurogenic regions are closed off to
form 1 part. Induction of neurogenic region by mesoderm takes place
3. Neurogenisis starts: three germ layers start to form in neuroblasts. Neuroblasts give rise to
ganglion mother cells and more neuroblasts.

Delamination = movement of neurogenic region to the interior side.

Involution = sheet of cells (mesoderm) moving inwards then migrate underneath the neurogenic
regions, leading to induction.

Ectodermal development is called neurulation. The neurogenic regions form the neural plate and
give rise to neural tissue. (the outer parts of the plate move towards eachother forming a tube) =
neurulation.

Notochord= mesodermal tissue that defines the body axes.

Neurulation process:

-The neural plate begins to roll up, forms the walls which fuse (close off) at the dorsal parts to form
the neural tube

-The mesoderm forms the tube called notochord which induces the neural tube.

-A group of cells called neural crest arises at the point of fusion of the neural tube

Experiments:

Induction of the neural tissue

-Isolation of fragments of embryo’s at different developmental stages shows when tissue becomes
committed tot he neural lineage.
1. Isolate the animal cap as it contains the neurogenic region (before gastrulation, during, and after)
2. Analyse what type of cells they form into.

Conclusion: During gastrulation the animal cap forms into neural tissue in a dish, stating that
induction takes place during the gastrulation process.

,Transplantation to reveal interactions with neighbouring tissues in making neural tissue

1. Transplant dorsal blastopore lipfrom a pigmented embryo to a non-pigmented embryo
2. When it is already induced it can form a new body axis in the host
3. When you place the dorsal blastopore lip to another place in the host, a second neural tube forms.

Conclusion: transplantation of the blastopore to a new host leads to formation of a neural tube at a
different part in the embryo, forming a second body axis.

Determination of ectoderm during gastrulation

1. When tissues are transferres between early gastrulas, the epidermal is formed, so no induction has
taken place. No second neural plate is formed in the host.
2. Whenusing late-gastrula tissues, two neural plates are formed in the host.

Conclusion: Late gastrula cells are determined, as early gastrula cells are not yet determined.

The molecular nature of the neural inducer

1. Isolate the ectoderm from the mesoderm -> Nothing happens
2.Remove only the mesoderm, so the ectoderm and endoderm are connected -> New mesoderm
forms

Conclusion: Endoderm gives signal for the induction of mesoderm

Indirect induction of neural tissue

1. Take the ectoderm and add the signal molecules from the endoderm that induce mesoderm
2. Mesoderm is formed and induction of ectoderm continues -> Neural tissue forms
3. Add neural inducing molecules directly to the ectoderm -> Neural tissue forms
examples Of neural inducers are follistatin, nogging and chordin

Actin binds to follistatin, blocking the receptor for normal signal induction -> Neural tissue forms
Speculation: Neural inducers work by inhibiting default pathways

Analysing the pathway of neural inducers

1. Isolate the animal cap
2. Put it with cells intact in a clump in a petridish -> Cells become epidermis
3. Put them dissociated in a petridish -> Cells become neural tissue
4. Put them dissociated +BMP4 -> Cells become epidermis again

Conclusion: Dissociation in culture (so placing them more widely spread on the dish) of animal cap
cells prior to gastrulation causes most of them to differentiate into neurons. This result supports the
hypothesis that the neural fate is actively suppressed by cellular associations in the ectoderm. BMP4

, is a surpressor molecule that needs to be interupted in order for neural tissue to form.

Chordin, nogging and follistatin all interfere with the activation of BMP receptor, inducing neural
induction only if the mesoderm is close enough to the neural region.

H2- Polarity and segmentation
Rhombomeres are repeated morphological subdivisions of the hindbrain.

Hox-gene expression specify different structures along the anterior -posterior axis of animals. The
specificity of Hox-genes function is determined by each gene conrolling the expression of different
groups of downstream genes. Higher levels of retinoic acid surpress Hox-genes.

Morphogenic induction of regions by soluble molecules the brain releases in gradients at certain
times in development. Exp:
-BMP’s
-FGF’s
-SHH’s
-WNT’s

Ectopic = abnormal expression or forming of tissue. (Out of its normal place)

Prosomeres= Give rise to the forebrain
Caudal = Tail of a body
Rostal = head of the body

Dorsal-ventral polarity:
Because the concentration shh is higher in the ventral region, only motor neurons will be formed in
the ventral plate.

Because the concentration BMP is higher in the dorsal region, only sensory neurons will be formed in
the dorsal plate.

BMP is expressed in the overlying ectoderm, activating the dorsal region (roofplate), leading to BMP
also being expressed by the dorsal region.

Neural crest cells can migrate in different directions. Because of the different directions, the crest
cells receive different signal during migration. About 80% neural crest cells turn into neural
peripheral systems. The rest form into pigment cells.

Experiments:

Master controle gene Pax6 experiments
-Pax6 mutant -> eye of the embryo is not developed well
-Pax6 + green fluorescent to analyze where it is expressed in the embryo-> in the forebrain

Dorsal-ventral polarity in the neural tube

1.Use a yellow marker for motor neurons
2. Remove the notochord -> No floor plate and no motor neurons

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