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"Epigenetic regulation of cortical neurogenesis and neural fates"
Kenneth Kwan, Assistant Professor, Department of Human Genetics, University of Michigan
The six-layered cerebral neocortex is assembled from diverse neuronal subtypes characterized by layer-dependent properties. To attain the laminar organization and neuronal diversity that support cortical circuit function, the full repertoire of distinct cell fates must be specified during neurogenesis. In the developing cortex, myriad subtypes of excitatory neurons arise from common neural progenitor cells that transition through distinct modes of cell production, sequentially specifying diverse cell types with a stereotyped temporal progression (deep-layer neurons → upper-layer neurons → astrocytes). The mechanisms underlying this sequential, stage-dependent generation of cell types must be capable of accounting for the previous mode of cell production to determine subsequent modes of genesis. This phenomenon is likely to involve epigenetic regulation, as daughter progenitors inherit from parent progenitors the same genome but distinct transcriptional landscapes appropriate for their stage in the neuro-gliogenic sequence. This work examines the roles of the polycomb repressive complex in the regulation of sequential cortical neurogenesis and cell fates.