Christopher A. Walsh, M.D., Ph.D.
Bullard Professor of Pediatrics and Neurology
Investigator, Howard Hughes Medical Institute
Division of Genetics
Center for Life Science, Room 15064
3 Blackfan Circle
Boston, MA 02115
Visit my lab page here.
We are interested in fundamental molecular mechanisms governing development and function of the human cerebral cortex. The cortex is the largest structure in the brain, essential for the intellectual functions that we humans pride ourselves on. Whereas the cortex is complex, it provides several advantages as a genetic system for studying neuronal development:
1. Neurons of the cortex are not formed in the cortex itself; instead, they are derived from dividing progenitor cells restricted to proliferative regions outside the cortex. The progenitor cells form post-mitotic cortical neurons in a fixed sequence.
2. Post mitotic cortical cells migrate long distances away from the proliferating cells into the cortex before differentiating. Therefore, steps of mitotic and post mitotic neuronal development occur in different places.
3. Human mutations disrupt particular steps of human cortical development in stunningly diverse and specific ways. These genetic diseases cause many childhood brain disorders, including developmental brain malformations, many forms of cognitive and intellectual disability, autism spectrum disorders, epilepsy, cerebral palsy and others.
4. Since brain evolution occurs by changes in specific genes, it is not surprising that some of the genes essential for human cortical development and function show evidence that they were targets of the evolutionary selection that shaped the size, shape, and function of the human brain.
We have used genetic and high-throughput DNA sequencing methods to identify genes underlying more than a dozen human brain disorders affecting stem cell proliferation, neuronal migration, neuronal differentiation, axon outgrowth, synaptic function, and other processes. Recent work has examined the significance of genomic differences between single neurons in human brain--caused by spontaneous mutation, copy number variation, or mobilization of endogenous retrotransposons—for normal brain development and for disease. Ongoing work analyzes the functional roles of selected human genes in shaping human brain structure and function, and studies other human genetic syndromes to identify additional genes required for cortical development.
For a complete listing of publications click here.
Last Update: 11/7/2013