Neurodevelopment KW2 V
Lecture 1
Development of the nervous system:
1. Neural induction
2. Polarity and Segmentation
3. Neurogenesis and Migration
4. Determination and differentiation
5. Axon Growth and Guidance
6. Target Selection
7. Naturally occurring neuron death
8. Synapse Formation and Function
9. Refinement of Synaptic Connections
Neural induction
▪ Evolutionary perspectives: what is interesting to know is that expect for
these colonial flagellates, everything else (all type of cellular organism)
have a type of neuron. They all have more of less the same shape →
elongated. Most of these were electrical and some of them (little bit later
in time), electron synapses coexist with chemical synapses.
→ Keep in mind that the basic building plan is the same for all species. Because
of evolution it will become more complex. Initially we all look alike in
development.
Depending on the outside world (what is the need), what need an animal to survive. We use
several animal models. Why? We are all differently in the outside world, so differences in
behaviour are steered by the nervous system. And you need to behave according to what is
needed. Need to survive can be different for each single species.
▪ Derivation of neural tissue: where does this nervous tissue come from?
Of all the things that we distinguish in our human body, derives from the exact same lineage
as our skin. The other half of that particular lineage, ectoderm in fact the central nervous
system.
Gastrulation: process where we will get the three germ layers. Endoderm, Mesoderm and
Ectoderm. Ectoderm = most important because gives rise to the central nervous system. But
also, to cell skin.
Neurulation = Ectodermal development in regard to nervous tissue.
,Hydra. Here you can see that is indeed very close to this outer lineage skin. If we zoom in,
the outer surface of this Hydra you can see the gastrodermis (inside) and the Epidermis
(outside). We have sensory cells and we have neurons. They are from the same lineage, but
these wiggles themselves out of the epidermis. They start of as the same cells. They go to the
inside, and they will make a network of neurons on the inside.
→ Underlaying the fact that both skin as well as central nervous system are derived from the
same batch.
C. Elegans. Very simple organism. Here also you can see that initially, in development, it
always starts off with proliferation (division of the cells). In these species it is called
blastomeres. P0 zero blastomere which divides in two AB blastomere and B1 blastomere.
→ AB blastomere will devide and devide and devide and then it will derive into skin
structures as well as neurons.
Red blastomeres will move to the outer rim. Then this C. elegans will go into proliferation
phase, division of those cells. And then you make a cross-section. What will you see? The
outer rim, which consists epidermal intermingle with neuron cells. And over time, these
neuron cells (dark red cells), they will squeeze themselves out of the epidermis to this inside.
And there they will become neurons which will make neurophenats.
,Drosophila. This is a very early drosophila embryo. In red you have then ventral natural part
that will eventually develop into the nervous system. If we make a cross section again right in
the middle. You still see more or less ventral right in the middle, and over time gastrulation
will kick in, in order to get this free mesoderm.
Invagination (like pushing into balloon) of the ventral furrow → cellular migration process
into the embryo. And you end up with this ring of mesoderm. And know of course this
neurogenic region used to be on the lateral side and know connected / fused at ventral of the
embryo.
→ these cells that used to be on de
lateral side are now connected and will
make the ventral neurogenic region.
→ From there neurons will wiggle
themselves into inner embryo.
Then as time proceed, there will be neurogenesis (division of the neurons), and these
neuroblast will move to the inner embryo. (initially, they were at the same level at the
epidermis and they will wiggle themselves into the interior of the embryo and they will make
nerve cords.
As time proceeds these neuroblasts divide and it will make ganglion mother cells (GMC).
They will eventually give rise to both neurons as well as ganglion cells.
→ Within the nervous system there are neurons and glial cells.
, Too zoom in:
Mesoderm, epidermis, neurogenic region. If we
enlarge this cell layer, you have epidermal cells
together with neurogenic cells. These
neurogenic cells tend to get a little bit bigger,
and sort of squeeze themselves out of this cell
layer to the inside of the embryo. This occurs in
several rounds. Within this nerve cord they are
still neurogenic → still divide. Initially
neuroblast will fist give rise to Ganglion mother
cells (GMC) (typical for drosophila). After that
there will be differentiation.
If we take one more step further. Here you have one big bowl of cells undergoes this
gastrulation process by this
Empty space is important to prevent gastrulation, to prevent cell movement. In the case of
Xenopus, that you have an involuting marginal zone (MZ), you see that the blue cells start to
migrate inwards. Why is this important? Only because this cell layer is able to communicate
with the other overlaying ectoderm, you will get neuroectoderm. Why? Because now they are
in close contact and now, they are able to induce the overlaying ectoderm.
Most proximal part will become the brain, most posttrial part will become spinal cord.
→ Mesodermal tissue that is underlaying ectoderm, is the tissue that is able to induce
ectoderm to become neuroectoderm.
▪ Induction of the neural tissue:
Notochord: specialisation of the mesoderm, defines the body axes. Because, the notochord is
over the complete lengths of your body. If will make sure that the overlaying ectoderm will