Molecular contributions to cerebral cortical specification

Evidence is accumulating that decisions of cell fate and commitment to specific regional phenotypes in the cerebral cortex occur through cell interactions that likely begin early in development, perhaps in the proliferative zone. We have focused on the development of the limbic cortex in rats, which includes areas involved in both cognitive and autonomic functions and is marked by expression of the limbic system-associated membrane protein. Transplantation studies show that precursor cells are sensitive to environmental cues which can control expression of area-specific phenotypes, including limbic system-associated protein synthesis and connectivity patterns, but early postmitotic neurons faithfully express traits based on their origin in the donor. We have studied this sensitive period of decision making in vitro. Molecules from the epidermal growth factor family influence dramatically the fate of precursor cells, but only in the presence of matrix molecules. In vivo, both the epidermal growth factor receptor and collagen type IV are expressed in the progenitor cell pool indicating that they can directly affect the initial decisions in differentiation. We suggest that early patterns of gene expression, influenced by environmental cues, are likely to provide a specific framework for subsequent decisions that lead to establishing cortical areas.