Click here to view some of Dr. Fishell's most recent work

Autism and Developmental Disorders Colloquium Series

 “Perspectives on the developmental origins of cortical interneuron diversity”

Gordon Fishell, Ph.D.
Professor, Developmental Genetics Program, Skirball Institute and Department of Cell Biology, NYU School of Medicine

6:00 p.m., Wednesday, February 6, 2008
MIT Building 46-3002 (auditorium), followed by a reception

Building Address: 43 Vassar Street, Cambridge, MA 02139

Hosted by Li-Huei Tsai, Ph.D., and the Brain Development and Disorders Project at MIT

Supported by the Simons Foundation and the Anne and Paul Marcus Family Foundation

Colloquia sponsored by the Autism Consortium

Please RSVP to lmavros@mit.edu

Cortical gabergic interneurons in mice are largely derived from the subpallium. Work from our laboratory and others over the past five years has demonstrated that a developmental logic in space and time underlies the emergence of specific cortical interneuronal subtypes. Following on the seminal work of the Rubenstein laboratory (Anderson et al., 1997a, b), we set out to fate map the output of the subpallial ganglionic eminences. Our initial approach utilized ultrasound backscatter microscopy to perform homotopic and heterotopic transplants of genetically marked progenitors from the lateral, medial and caudal ganglionic eminences (LGE, MGE and CGE respectively) to unmarked host brains (Wichterle et al., 2001; Nery et al., 2002, Butt et al., 2005). The LGE at least in the context of our transplant studies did not appear to generate cortical interneurons. By contrast, we found that that approximately eighty percent of cortical interneurons arise from the MGE, while the remaining twenty percent was generated by the CGE. Hence, the majority of interneuron subtypes, including all fast spiking parvalbumin-positive basket cells and somatostatin-positive Martinotti cells appear to arise from the MGE. A more restricted set of cortical interneurons seems to be generated in the CGE, the majority of which are bipolar calretinin/VIP-positive interneurons. Complementing these results, we have recently demonstrated using inducible genetic fate mapping that the MGE produces specific cortical interneuron subtypes at discrete timepoints during development (Miyoshi et al., 2007). These studies demonstrate that cortical interneurons arise from a precise developmental program that acts in both space and time. Beyond this however, it seems likely that postmitotic events influence the specific function of subclasses of cortical interneurons. A primary challenge in the future will be determining what aspects of interneuron diversity are determined by intrinsic genetic programs within each lineage versus those properties imposed by the local environment in the cortex.