STEM-CELLS IN THE EMBRYONIC CEREBRAL-CORTEX - THEIR ROLE IN HISTOGENESIS AND PATTERNING

The cytoarchitectural simplicity of the cerebral cortex makes it an at tractive system to study central nervous system (CNS) histogenesis-the process whereby diverse cells are generated in the right numbers at t he appropriate place and time. Recently, multipotent stem cells have b een implicated in this process, as progenitor cells for diverse types of cortical neurons and glia. Continuous analysis of stem cell clone d evelopment reveals stereotyped division patterns within their lineage trees, highly reminiscent of neural lineage trees in arthropods and Ca enorhabditis elegans. Given that these division patterns play a critic al part in generating diverse neural types in invertebrates, we specul ate that they play a similar role in the cortex. Because stereotyped l ineage trees can be observed from cells growing at clonal density, cel l-intrinsic factors are likely to have a key role in stem cell behavio r. Cortical stem cells also respond to environmental signals to alter the types of cells they generate, providing the means for feedback reg ulation on the germinal zone. Evidence is accumulating that cortical s tem cells, influenced by intrinsic programs and environmental signals, actually change with development-for example, by reducing the number and types of neurons they produce. Age-related changes in the stem cel l population may have a critical role in orchestrating development; wh ether these cells truly self-renew is a point of discussion. In summar y, we propose that cortical stem cells are the focus of regulatory mec hanisms central to the development of the cortical cytoarchitecture. ( C) 1998 John Wiley & Sons, Inc.