Cell Migration in the Developing Nervous System PDF

BIO344 Development of the Nervous System Cell migration in the developing nervous system Esther Stoeckli Proliferation Differentiation Cell migration Axonal pathfinding Connectivity Synapse formation Circuit formation...

BIO344 Development of the Nervous System Cell migration in the developing nervous system Esther Stoeckli Proliferation Differentiation Cell migration Axonal pathfinding Connectivity Synapse formation Circuit formation Cell death Maturation Pruning Aberrant development can lead to disease Neural crest cells give rise to the PNS Neural plate border specification Neural crest specification Neural crest epithelial to mesenchymal transition (EMT) / delamination Neural crest migration from: Martik & Bronner Trends in Genetics (2017) 33: 715-727 Neural crest cells and their derivatives Cranial Bone and cartilage Connective tissues (teeth, eyes, ears) Sensory neurons Glial cells Melanocytes Vagal Enteric neurons Sensory neurons Glial cells Melanocytes Smooth muscle Cardiac tissues Trunk Sensory neurons Autonomic neurons Chromaffin cells (adrenal medulla) Glial cells Melanocytes Also in the CNS, some precursor cells migrate long distances to reach their final destination Development of the Cerebral Cortex Migration Proliferation VZ: Ventricular Zone I-VI: Cortical Layers WM: White Matter SVZ: Subventricular Zone Time decides on the formation of neurons versus glia cells Sokpor et al., front. neurosci. 2022 Radial glia cells are the stem cells of the developing cortex Higginbotham et al., Cerebral Cortex 2011 Glia-Guided Locomotion Cajal Retzius Cells Release Reelin as Stop Signal for Migrating Precursors Apical progenitors /radial glia cells divide asymmetrically to self renew and generate precursor cells Sokpor et al., front. neurosci. 2022 Inside-Out Development of the Cortical Plate Birthdating with [3H]-Thymidine Birthdating with [3H]-Thymidine (Monkey) Evolutionary aspects of corticogenesis Taverna et al., Annu. Rev. Cell Dev. Biol. 30(2014)465 Additional neurons required for the primate cortex are generated in the outer subventricular zone Fietz and Huttner, Curr. Opin. Neurobiol. 2011 The occurrence of basal radial glia cells in the outer subventricular zone allows for a substantial expansion of neuronal cell number Florio et al., 2017  The basic principles of corticogenesis are conserved between rodents and primates Cadwell et al., Neuron 103(2019)980  …but timing and cell-type complexity have increased during evolution Cadwell et al., Neuron 103(2019)980  …but timing and cell-type complexity have increased during evolution Cadwell et al., Neuron 103(2019)980  The basic arrangement of cortical areas is preserved thalamocortical pathways targeting specific areas in the cortex Cadwell et al., Neuron 103(2019)980 Interneurons form synapses with different parts of excitatory neurons PV Parvalbumin SST Somatostatin VIP Vasoactive Intestinal Peptide RELN Reelin Wamsley & Fishell, 2017 Diversity of GABAergic Interneurons in the Neocortex from: Lim et al. Neuron (2018) 100:294-313 Interneurons originate in the medial, caudal, or lateral ganglionic eminence Wamsley & Fishell, 2017  Guidance cues and neuronal migration in the telencephalon Toudji et al., Front. Neural Circuits, 2023 | https://doi.org/10.3389/fncir.2023.1256455 Ventricle-directed migration precedes layer-specific targeting of interneurons Naradarajah and Parnavelas, Nat.Rev. Neurosci 3(2002)423 Milestones in the Development of Cortical Interneurons Example: Developmental of SST+ Martinotti cells MGE: medial ganglionic eminence NCx: neocortex SVZ: subventricular zone VZ: ventricular zone : neuronal activity-dependent from: Lim et al. Neuron (2018) 100:294-313 Cortical Migration Defects Bielas et al. Annu. Rev. Cell Dev. Biol. 20(2004)593–618 Cortical Migration Defects Human Disorder: Periventricular Heterotopia Mutated Genes: - filamin A (FLNA) => actin-binding protein - Arfgef2 => vesicle trafficking - etc  Cortical Migration Defects Normal Human Disorder: Lissencephaly / Subcortical Band Heterotopia (Double cortex) Mutated Genes: Dcx, Lis1, etc. Cortical Migration Defects Mutated Gene: Reelin (RELN) Reeler mice show aberrant layering of the cortex Cortical Migration Defects Human Disorder: Cobblestone Lissencephaly Mutated Gene: - POMT1 - POMGnT1 - Fukutin Migration in the Developing Cerebellum  Migration in the Developing Cerebellum Granule neuron precursors migrate rostrally, Precerebellar nuclei precursors migrate ventrally EGL: external granule layer IGL: internal granular layer VZ: ventricular zone ML: molecular layer The cerebellum originates from the wall of the ventricle: the rhombic lip Granule cell precursors stop dividing in the inner EGL and start to send out parallel fibers before migrating to the IGL Butts et al., Development (2014)4031 Granule cell precursors downregulate Sema6A to start radial migration to the inner granule cell layer Chédotal, 2010 Granule cells send out parallel fibers before they start migrating along Bergmann glia fibers towards the prospective IGL Xu et al., Molecular Neurobiology 47(2013)833 Cerebellar development is accomplished 3 weeks after birth in mouse Goldowitz and Hamre, TINS 1998 Glutamatergic and GABAergic neurons have different origins Marzban et al. Frontiers Cell. Neuro 8(2015)450 Cellular connectivity of the cerebellum PN Purkinje cell SC Stellate cell GCN Granule cell MF Mossy Fiber DCN Deep Cerebellar Nuclei CF Climing Fiber BC Basket cell ML Molecular layer PL Purkinje cell layer GL Granular layer Iulianella et al., Dev Dynamics 2019 https://doi.org/10.1002/dvdy.64 Migration of neuronal precursor cells during brain development Cerebral cortex: A. Radial migration Formation of excitatory pyramidal neurons in the cortex At least two major migration modes: - somal translocation (early in development) - glial guided locomotion along radial glia B. Tangential migration Immigration of inhibitory interneurons into the cortex Cerebellum: A. Radial migration of Purkinje precursor cells B. Tangential migration of cerebellar granule cell precursors Next week: Lukas Sommer Neural Crest Cells