John Rubenstein, MD, PhD

Genetic Regulation of Forebrain Development

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.

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. SHH and FGF8) or encoding transcription factors that transduce patterning signals (e.g. Coup, Gsx, Nkx and Pax6).

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. Dlx1, Lhx6, Npas1, and Zfhx1b) or cerebral cortex (e.g. COUP, Pbx1 and Tbr1). These studies are providing insights into the specification and differentiation of distinct types of neurons (Glutamatergic, GABAergic and Cholinergic). Within the basal ganglia, where GABAergic neurons are produced, subsets of these cells migrate tangentially to different destinations including the cerebral cortex. We are investigating the regulation of these tangential migrations and have evidence that neuropilin-semaphorin and cytokine signaling plays a key role in this process.

Finally, we are beginning to study the mechanisms that regulate the formation of circuitry within the forebrain. Our long-term aims are to understand the genetic underpinnings of forebrain evolution and function and to help elucidate mechanisms underlying human neurodevelopmental disorders. 

Lab Members

Lab Website

Academic community service and committee membership:

NS Student Advisors/Student Progress committee, Advisor to first-year neuroscience students, and occasionally more senior students, Psychiatry Appointments and Promotions Committee