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John Rubenstein, MD, PhD

John Rubenstein, MD, PhD
Professor, Department of Psychiatry
Research Summary:
Genetic Regulation of Regional Specification and Differentiation in the Forebrain
Our laboratory has several types of projects:

Forebrain patterning centers:
We investigate regions of the neural plate and neural tube that produce secreted factors that control regionalization and growth of the forebrain. Foremost in this arena have been our studies on Fgf8, Fgf15, Fgf17 function in regionalization of the neural plate and cerebral cortex. This work has opened the door to elucidating the genetic circuitry of prefrontal cortex development.

Transcription factors that control regional specification of brain subdivisions: Ongoing studies focus on defining the transcription factors that control CNS development. These include the roles of the Nkx genes in specifying ventral neural progenitors (e.g. Nkx2.1 for globus pallidus principal neurons and cortical interneurons). These results are contributing towards elucidating the transcription factor code that defines the development programs of forebrain progenitor zones.

Transcription factors that control and cell-type differentiation:
In this regard, we currently focus on the differentiation of forebrain GABAergic neurons, and the functions of the Dlx1, 2, 5 & 6, and Lhx6 & 8 transcription factors.

Dlx Transcription factors that control craniofacial patterning:
Studies of Dlx function in craniofacial neural crest have illuminated the role of these genes in patterning the jaw and middle ear skeleton, findings that have important evolutionary and medical ramifications.

Cortical inhibitory neurons
are generated in the basal ganglia and tangentially migrate to the cortex: We are currently defining the molecular mechanisms that control the movement and integration of the migratory cells to their destinations. We are also learning how Dlx function in neurons controls their function and survival. With Arturo Alvarez-Buylla, Scott Baraban and Arnold Kriegstein, we are developing methods for interneuron transplantation to treat forebrain disorders, such as epilepsies.

Neuropsychiatric Disorders (Autism):
The lab has a longstanding clinical interest in Autism. Ongoing studies involve sequencing of candidate genes, and functional analyses of mutant alleles.

Selected Publications

Storm E, Garel S, Borello U, Hebert JM, Martinez S, McConnell S, Martin G and Rubenstein J. (2006) Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers. Development. 133(9):1831-1844.

Cholfin J and Rubenstein JLR (2007) Patterning of frontal cortex subdivisions by Fgf17. PNAS. 1;104(18):7652-7657.

Cobos I, Borello U, Rubenstein JLR. (2007) Dlx transcription factors promote migration through repression of axon and dendrite growth. Neuron. 54, 873–888.

Petryniak MA, Potter GB, Rowitch DH, Rubenstein JL. (2007) Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Neuron. 2007 55(3):417-433.

Faedo A, Tomassy GS, Ruan Y, Teichmann H, Krauss S, Pleasure SJ, Tsai SY, Tsai MJ, Studer M, Rubenstein JL. (2008) COUP-TFI Coordinates Cortical Patterning, Neurogenesis, and Laminar Fate and Modulates MAPK/ERK, AKT, and {beta}-Catenin Signaling. Cereb Cortex. 18(9):2117-31.