bFGF, neurotrophins, and the control of cortical neurogenesis

Early in development, the cerebral cortical epithelium consists of a thin sheet of columnar neuroectoderm cells. This germinal layer, the ventricular zone (VZ), proliferates extensively and generates immature neurons that migrate toward the pial surface, laying down the preplate and then the cortical plate from which the mature cortical layers derive. The earliest born neurons populate deeper cortical layers, with later born neurons populating the more superficial layers. This initial period of embryonic neurogenesis is followed by the largely postnatal production of glial cells, the majority of which derive from a second germinal layer, the subventricular zone, which persists into adulthood in some cortical regions. In part of the cortex, the hippocam-pus, neurogenesis is extended into the postnatal period. Factors that regulate the proliferation and differentiation of neuroectoderm cells, and the timing of these processes, are critical for normal cortical development. With the establishment of in vitro systems that allow the division and differentiation of neuroectoderm cells in culture, and with the advent of techniques that probe the role of factors during CNS development in vivo, researchers are beginning to examine the characteristics of developing neuroec-toderm cells and investigate how their proliferation and differentiation may be regulated. In a recent issue of Neu-ron, two papers converge in their finding that, for the cere-bral cortex (Ghosh and Greenberg, 1995) and hippocam-pus (Vicario-Abejbn et al., 1995), basic fibroblast growth factor (bFGF, also known as FG F2) and neurotrophins may interact to regulate division and differentiation of neuroec-toderm cells. How Are Neurons Generated in the Cerebral Cortex? The CNS neuroectoderm has been described classically as an overtly homogeneous layer of cells. Studies have not distinguished differences that allow prediction of cell fate based on neuroectoderm cell morphology. A number of recent studies indicate, however, that at any one time in development the neuroectoderm cells in a given CNS region may be heterogeneous. In the cerebral cortex, ret-roviral lineage studies conducted in vivo or in mass cultures in vitro reveal that the majority of clones consist of one cell type, either pyramidal or nonpyramidal neurons, or astrocytes or oligodendrocytes (reviewed in Kilpatrick et al., 1995). These findings suggest that heterogeneous progenitor cells coexist in the cortical VZ, although the possibility that different microenvironments are instructive for cell fate cannot be entirely ruled out. In clonal analyses of cells developing under standardized culture conditions, where the environment is as near identical for each cell as …