Lecture 12- Neuronal migration in brain development III (cerebellum and RMS) Flashcards
What are the main functions of the cerebellum?
-coordinates motor patterns by monitoring and modifying motor programs
What percentage of all the neurons in the brain are in the cerebellum?
- 50%
- arranged in a highly ordered fashion
What are the cell types in the cerebellum? (4)
- Purkinje cells (PC)
- Granule cells (GC)
- Stellate cells (S)
- Golgi epithelial cells (GEC)
What are the three layers of the cerebellum?
- Molecular layer (ML)
- Purkinje cell layer (PCL)
- Granular layer (GL)
- cerebellum has laminated structure so needs migration during development
What are the Purkinje cells?
-projection neurons and the other layers contain various interneurons (stellate, granule, basket and golgi epithelial cell)
When does the cerebellum (cerebellar cortex) undergo morphogenetic changes?
-during development from E11 to postnatal day (P) 7
- tiny structure between midbrain and hindbrain at first (the cerebellum) then grows
- P- postnatal (birth)
- the adult picture= granular cell layer is darkly stained(in adult called inner granular layer)
- the migration occurs P0-P7 so after birth
What is the cerebellum derived from?
- from the rhombic lip situated in the dorsal metencephalon (hindbrain) adjacent to the fourth ventricle
- this layer of tissue that gives rise to the cerebellum is called external germinal layer
What is the external germinal layer (EGL)?
- this layer generates granule cells that migrate inwardly in a radial manner with the assistance of radial glia fibers of the Golgi epithelial cells
- the EGL is a transitory developmental structure not present in the adult
- this is involved in the development of the cerebellum
What are the domains of the developing cerebellum? (5)
- the developing cerebellum can be subdivided into domains:
1. External granule (germinal) layer
2. Molecular layer
3. Purkinje cell layer
4. Internal granule cell layer
5. Ventricular zone
What are the two zones in the developing cerebellum where cells are generated and what cells are born where?
- Ventricular zone= Purkinje cells are born here
- External granule (germinal zone)= Inhibitory granule neurons born here
What is the Purkinje cell migration in the cerebellum like?
-they are born in the ventricular zone and migrate outward
What is the migration of inhibitory granule neurons in the developing cerebellum like?
- born in the external granule layer (EGL)
- migrate through the molecular layer past the Purkinje cells to form the internal granule layer
- so during development have two granule layers, as and adult only he internal one remains
What do defects in the VLDLR gene lead to?
- pontocerebellar hypoplasia
- cerebellum shrinks and often doesn’t form at all
Does Lissencephaly have an effect on the cerebellum?
- yes
- when mutations in RELN (gene coding for Reelin) then big defects in the cerebellar lamination and formation
What are the mutants shown in the picture?
scm= scrambler is a natural mutant of the Dab1 protein
A= +/scm: heterozygote, control
B= scm/scm: Dab1 null mutant
C= rl/rl: Reelin null mutant
D and E compare the effects of B and C- very similar, thus Dab1 and Reelin are part of the same pathway
- Dab is an intracellular adaptor molecule for Reelin signalling
- these mutations lead to significant defects in the cerebellum
What are the two cerebellar abnormalities that Reelin mutations lead to?
- Purkinje cells form clumps and not a single layer
- Granule cells remain in the external layer and do not migrate past the Purkinje cells
What is the role of Reelin in cerebellar neuronal migration?
- Reelin released by external granule layer situated on the outer part.= Purkinje cells migrate towards these cells
- This is very similar to the cortex where Reelin is expressed by Cajal Retzius cells in the Marginal Zone (only similar to the Purkinje cell migration)
- in the cerebellum have cell moving towards reelin (Purkinje cells) and away from it (granule cells)
- when Reelin is absent the migration does not occur
- Reelin provides orientation cues