John Rubenstein, MD, PhD


The embryonic neural tube differentiates into diverse structures depending upon their spatial coordinates within the embryo. The forebrain, which is at the rostral end of the neural tube, differentiates into the cerebral cortex, the basal ganglia and other components, each with distinct histologies and functions. Our laboratory is interested in studying the genes that regulate regional specification and differentiation of the mammalian forebrain particularly within the cerebral cortex and basal ganglia. Analysis of the expression of regulatory genes has proven to be a useful method to define functional subdivisions of the forebrain. These studies have led us to propose that the vertebrate forebrain is subdivided by longitudinal and transverse boundaries. We are investigating the inductive mechanisms that pattern the neural plate and neural tube, by analyzing the phenotypes of mice with mutations in genes encoding patterning molecules (e.g. Fgf8, Fgf17) or encoding transcription factors that transduce patterning signals (e.g. Gsh2 and Nkx2.1). To study neurogenesis, differentiation and migration within the forebrain we have been analyzing mouse mutants for several transcription factor genes that are expressed in the primordia of the basal ganglia (e.g. Dlx, Lhx, Mash and Pbx) or cerebral cortex (e.g. COUPTF1). These studies are providing insights into the specification and differentiation of distinct types of neurons (Glutamatergic, GABAergic and Cholinergic). We are interested in using the transcription factor code information to program progenitor cells into specific neuronal fates, so that one can consider generation of these cell types for therapies of brain disorders.