Neural Induction and Cellular Processes during Early Development Flashcards
What is a morphogen?
Signalling molecule that produces specific molecular/cellular responses based on its concentration
Morphogens influence cell fate in a time and space-dependent manner.
Name three morphogens involved in Anterior-Posterior Nervous System Patterning.
- Retinoic acid (RA)
- Fibroblast growth factor (FGF)
- Wnt
These morphogens play critical roles in the development of the nervous system.
What are the morphogens involved in Dorsal-Ventral Nervous System Patterning?
- Bone morphogenic protein (BMP)
- Noggin
- Chordin
- Sonic hedgehog (Shh)
BMP and its antagonists are crucial for establishing the dorsal-ventral axis.
What are organizers in the context of morphogens?
Small groups of cells that release patterning molecules (morphogens)
An example is the notochord, which is the first source of morphogens.
What role does the roof plate play in morphogen signaling?
Releases TGF-β family, BMPs, dorsalin, retinoic acid (RA), Noggin
The roof plate contributes to the dorsal-ventral patterning of the nervous system.
What is the function of the floorplate?
Secretes Sonic Hedgehog (Shh), retinoic acid (RA), Noggin, Chordin
The floorplate is crucial for the ventral patterning of the nervous system.
What is neurogenesis?
Birth of neurons from neural stem cells (NSCs)
Neurogenesis is primarily complete by birth, with exceptions in the SVZ and hippocampus.
What does the direction of the mitosis plane determine?
The type of cell division
The position of the mitotic spindle during mitosis influences whether the division is symmetric or asymmetric.
What happens during symmetric division?
Produces 2 identical cells (e.g., 2 neural epithelial cells or 2 radial glial cells)
This occurs before neurogenesis and contributes to pool expansion.
What characterizes asymmetric division?
Produces 2 different daughter cells (e.g., 1 radial glial cell + 1 neuron)
This leads to direct neurogenesis where the neuron does not divide again.
What is an intermediate progenitor cell (IPC)?
Progenitor that gives rise to a neuroblast, which then becomes a neuron
IPCs are not fully differentiated but are crucial in the neurogenesis process.
Describe the ‘inside-out’ manner of neuronal migration.
Deeper cortical layers are formed before more superficial ones
This pattern is observed during the development of the cortex.
What guidance mechanisms support neuronal migration?
- Radial glial cells (RGCs)
- ECM proteins (e.g., Reelin, Laminin)
- Integrin, LIS1, Neuregulin
These factors help neurons migrate to their appropriate layers.
What is the post-natal GABA switch?
GABA initially acts as excitatory, then becomes inhibitory upon reaching the cortex
This switch is caused by changes in transporter expression affecting chloride levels.
What is gliogenesis in the developing brain?
The process of forming glial cells, such as astrocytes, oligodendrocytes, and ependymal cells
Gliogenesis starts after neurogenesis and continues after birth.
Compare gliogenesis and neurogenesis.
Gliogenesis occurs later and is regulated differently than neurogenesis
Signalling and transcription factors determine cell fate in both processes.
What is the role of astrocytes in astrogliogenesis?
Derived from astrocyte precursors that are influenced by negative proneural bHLHs and positive Notch/Nrg signals
This process is part of gliogenesis.
What is myelination?
The process of forming a myelin sheath around neurons
Myelination starts soon after an increase in glial cell numbers and is rapid during the first year of life.
Which pathways myelinate first during development?
- Sensory pathways
- Motor pathways
- Association areas
This sequence reflects the developmental priorities of sensory and motor functions.
Neurogenesis genes
neg. Notch, pos. bLHLH gene products -> neuronal precursors -> neurons
Oligodendrogenesis genes
neg. Proneural bHLHs, pos. Olig ½ Nkx2.1 -> oligodendrocyte precursors -> oligodendrocytes
“tangential” migration
interneurons from the subpallial embryonic region (MGE) undergo this migration to reach their appropriate layers in the cortex
During mid-gestation (week 20, early infancy/pregnancy) and early infancy
Guidance for migration:
- RGCs
- SDF1, Neuregulins
RGCs (B cells)
generate neuroblasts that migrate in chains into the olfactory bulb, where they differentiate into interneurons
Migratory path = rostral migratory stream (RMS) more anteriorly
Astrocytes, oligodendrocytes and
ependymal cells also derive from RGCs
Hox gene expression:
divides the CNS into segments. Much of the neural tube (hindbrain, spinal cord) becomes divided into neuromeres (segments).
-Dictated by Homeobox genes
-Organized into 4 clusters
-Temporal AND spatial (A→P)- specific expression
-Contributes to neuronal identity
-Conserved mechanism
-Each segment, cell identity is determined by morphogen concentration and which hox genes are turned on and off
Somite
BMPs
Guidance for migration:
- RGCs
- ECM proteins (e.g. Reelin, Laminin);
Integrin, LIS1, Neuregulin
Post-natal GABA switch
In the embryonic brain: [Cl-]i is
relatively high, Cl- transport
dominated by NKCC1
- Depolarizing GABA: guides
proliferation, migration and
construction/maturation of circuits
* Post-natal: Cl-]i decreases, due to
increased expression and activity of
KCC2
- Hyperpolarizing GABA: fine-tunes
circuitry activity (e.g. increase
sensitivity to sensory input)
neuroblasts and their migratory path
generated by RGCs (B cells), migrate in chains into the olfactory bulb,
where they differentiate into
interneurons
Migratory path = rostral migratory stream (RMS)
radial glial cell shape
bipolar
order of differentiation
neuroepithelial cell -> radial glial cell -> neuron
migratory path of RGC
rostral migratory stream (RMS) more anteriorly
