LES 1: Nervous system development (Prof. Ellender)
Neurons connect within complex & extensive neuronal circuits
• Each distinct circuit often provides functionality (e.g.
sensory processing) and performs computations
➔ A lesion in a particular circuit that provides a certain
functionality can create a problem to that function
• Connectivity is complex and distinct and precise →
neurons really care where they connect to = precise
• Many circuits exhibit plasticity (i.e. interactions
between neurons can change) → to respond to the
external environment
• Can be locus of dysfunction (e.g. depression-related
behaviors)
WHEN AND HOW DO NEURONAL CIRCUITS EMERGE?
some species its circuits are quite advanced when it comes out of
the egg and is already functioning before it hatches
other species need a lot more neurodevelopment processes
plasticity refines the circuit
how does the environment shape te circuit?
Major Events in Nervous System and Circuit Development
1. Embryogenesis
2. Patterning
3. Proliferation & Neurogenesis
4. Apoptosis
5. Migration
6. Differentiation
7. Generating neuronal diversity–Making and refining synaptic connections
8. Progenitor origin and synapse specificity
Major early milestones in brain development
,Brain growth in chimpanzee and human
some species most of the development happens in utero and
stop after birth
look at size, chimp has most growth before birth. human have a
large amount of growth after birth (not necesarily more neurons,
more connections)
1. EMBRYOGENESIS
Where do cells of the brain come from?
oocyte --> fertilised --> movement of cells and interactions make
different germ layers --> gastrulation --> neuroinduction
(differentiate and become neuron tissue (comes from ectoderm)
--> neuroectoderm (outer layer)
FACTORS INVOLVED IN NEURAL IDUCTION
notachord (mesoderm) releases a factor and will
diffuse and activate cells around the notachord
(neuroectoderm) and push
NEURULATION = the process of the neural tube
formation (hollow tube of cells)
First, the neural plate folds up to form the neural
tube, then the neural tube closes in a posterior to
anterior gradient
THIS PROCES IS VERY COMPLEX SO A LOT CAN
GO WRONG!!
Failure of neural tube closure results in
severe malformations
Spina bifida = problems with the closure of the neuronal tube
Neural epithelium (tube) gives rise to entire adult nervous system and all its
circuits
initial monolayer of cells start deviding and makes the enormous complex
,DEVELOPMENT OF THE VENTRICULAR SYSTEM
fluid filled cavity = ventricular system
retina in your eye is neuroectoderm
lays outside of you scull
it develeops from the neuronal tube
2. Patterning
how do stem cells know which kind of neurons they have to make?
splitting of groups of cells from the neuronal tube with different functions
→ ‘Molecular and cellular specification of areas of developing tissue’
, sonic stays active even when the tube is closed
overlaying ectoderm induces the formation of neuronal crest cells (cells are born from the deviding)
Neural crest stem cells (blue) are generated in the dorsal region of the neural
tube where they undergo an epithelial mesenchymal transition, delaminate
and migrate into the periphery. The induction of these cells is regulated by a
combinatorial transcriptional code.
sonic is a ventalising factor
hox genes: the expression is regulated by diffusional factor
RA induce the expression of different expressions of hox genes
Interaction of morphogens and patterning
• Morphogen - a signaling molecule that acts at a distance to induce two or
more different types of tissue (e.g. retinoic acid, RA).
• Morphogens induce pattern formation.
• Response to a morphogen is altered by the previous patterning of a tissue
releaseble factors are mophogens and impact hte shape and size of later structure