Asymmetric cell division and the generation of cell diversity in the embryonic cerebral cortex.

摘要

The cytoarchitectural complexity yet organizational simplicity of the cerebral cortex makes it an intriguing system to study central nervous system (CNS) histogenesis—the process whereby diverse cells are generated in the right numbers at the appropriated place and time. How the orderly production of diverse cell types is achieved has been a key question for development biologists. Using an in vitro culture system, we performed clonal analysis and time-lapse video recording on cortical progenitor cells isolated from the embryonic mouse cerebral cortex at early stages. We found cortical progenitor cells generate neurons contributing to distinct cortical layers in the same temporal order as they do in vivo. Cortical stem cells continue the normal timing of cell type production by making neurons before glia. Hence distinct cortical cell types are made in temporal phases even from individual, isolated progenitor cells. This suggests that the normal order of cell production is largely intrinsically determined within the cells, although the environment may modulate it. During development, stem cells maintain the ability for self-renewal, but they undergo intrinsic changes in their capacity to produce neurons versus glia and in their responsiveness to EGF.