Cours: Neurodevelopmental Disorders

Cell Migration in the Developing Nervous System

• Cell migration is a crucial part of nervous system development.
• Cell migration in the developing nervous system involves different stages, including proliferation, differentiation, connectivity, maturation, and pruning.
• Aberrant development can lead to diseases.
• Neural crest cells contribute to the peripheral nervous system (PNS).
• Neural crest cells undergo specification, EMT/delamination, and migration.
• Neural crest cells give rise to cranial (bone, cartilage, connective tissue), vagal (enteric neurons, sensory neurons, glial cells, smooth muscle, cardiac tissue), and trunk (sensory neurons, autonomic neurons, chromaffin cells, glial cells, melanocytes) derivatives.
• Precursor cells in the central nervous system (CNS) migrate long distances to reach their final destinations.
• The development of the cerebral cortex involves proliferation and migration.
• Examples of proliferation stages are observed in E 8.5 in the ventricular zone (VZ).
• Migration is evident from the VZ to the cortical layers.
• Development of cortical and glial cells involves specific times and sequences.
• Radial glia cells are stem cells of the developing cortex.
• Radial glia undergo symmetric and asymmetric divisions, leading to gliogenesis.
• Radial glia cells guide neuronal migration.
• Cajal Retzius cells release Reelin as a stop signal for migrating precursors.
• Apical progenitors/radial glia cells divide asymmetrically to self-renew and generate precursor cells.
• Cortical plate development occurs from the inside out.
• Birthdating with [H]-Thymidine can be used to identify the time of origin of neurons.
• The basic arrangement of cortical areas in the brain is preserved across species.
• Interneurons form synapses with different parts of excitatory neurons.
• The diversity of GABAergic interneurons in the neocortex is essential for neural circuit function.
• Interneurons originate in the medial, caudal, or lateral ganglionic eminence.
• Guidance cues are essential for neuronal migration.
• Ventricle-directed migration precedes layer-specific targeting in interneurons.
• Milestones in cortical interneuron development include neurogenesis, tangential migration, laminar allocation, wiring, programmed cell death, and circuit refinement.
• Cortical migration defects can be categorized as initiation, ongoing migration, lamination, and stop signal defects.
• Reeler mice show aberrant layering of the cortex.
• Cobblestone lissencephaly is a human disorder associated with cortical migration defects.
• Cerebellar development involves granule neuron precursor migration and precerebellar nuclei precursors migration.
• Granule cells send out parallel fibers before migrating along Bergmann glia fibers.
• Cerebellar development is completed about three weeks after birth in mice.
• Glutamatergic and GABAergic neurons have different origins.
• Molecular connectivity in the cerebellum involves Purkinje cells, granule cells, and neurons.