BBS Faculty Member - Christopher Walsh

Christopher Walsh

Investigator, Howard Hughes Medical Institute
Chief, Division of Genetics and Genomics, Boston Children's Hospital
Bullard Professor of Pediatrics and Neurology

Boston Children's Hospital
CLS, Room 15064
3 Blackfan Circle
Boston, MA 02115
Tel: 617-919-2923
Fax: 617-919-2010
Lab Members: 9 postdoctoral fellows, 6 graduate students
Visit my lab page here.

Our lab is interested in fundamental 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. The cerebral cortex has to solve several problems during development: it must be correctly patterned, it must obtain the proper complement of cells of distinct types, and finally all those cells have to get wired up just right in order to work properly. 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; instead, they are derived from dividing cells located in specialized proliferative regions far away from the cortex

2] Postmitotic cortical cells migrate long distances away from the proliferating regions into the cortex before differentiating. Therefore, steps of mitotic and postmitotic neuronal development occur in different places.

3] A stunning diversity of mutations affect humans to disrupt specific steps in cortical development. Some mutations affect the structure—i.e., the size and shape--of the cerebral cortex, and often result in the accumulation of cortical cells in abnormal locations reflecting the site of action and the function of the gene involved. Other disorders produce a cortex with seemingly normal structure, but severely abnormal function. Together, these human mutations cause a host of important brain disorders including epilepsy, autism, intellectual disability, and some forms of cerebral palsy.

We have used direct genetic studies to identify dozens of genes required for the normal structural or functional development of the human cerebral cortex. An unexpected finding is that some genes essential for human cortical development were targets of evolutionary selection in the primate lineage leading to humans, suggesting that changes in some of these genes help define our brain as uniquely human. Recent work has developed technology for profiling and sequencing the genomes of single neurons from the human brain, to analyze disease-associated mutations that appear to be present in brain but not in other tissues, and that arise during normal brain development.

Last Update: 12/12/2016


For a complete listing of publications click here.



Poduri A, Evrony GD, Cai X, Walsh CA. Somatic mutation, genomic variation, and neurological disease. Science. 2013 Jul 5; 341(6141):1237758.
doi: 10.1126/science.1237758. Review. PMID: 23828942

Bae BI, Tietjen I, Atabay KD, Evrony GD, Johnson MB, Asare E, Wang PP, Murayama AY, Im K, Lisgo SN, Overman L, Šestan N, Chang BS, Barkovich AJ, Grant PE, Topçu M, Politsky J, Okano H, Piao X, Walsh CA. Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning.
Science 2014 Feb 14; 343 (6172):764-8. doi: 10.1126/science.1244392. PMID:

Lodato* MA, Woodworth* MB, Lee* S, Evrony GD, Mehta BK, Karger A, Lee S, Chittenden TW, D'Gama AM, Cai X, Luquette LJ, Lee E, Park+ PJ, Walsh+ CA. Somatic mutation in single human neurons tracks developmental and transcriptional history.
Science. 2015 Oct 2;350(6256):94-8. doi: 10.1126/science.aab1785. PMID: 26430121  (*,+ equal contribution) [cover illustration]

Zhang X, Chen MH, Wu X, Kodani A, Fan J, Doan R, Ozawa M, Ma J, Yoshida N, Reiter JF, Black DL, Kharchenko PV, Sharp PA, Walsh CA. Cell type-specific alternative splicing governs cell fate in the developing cerebral cortex.
Cell. 2016 Aug 25;166(5):1147-1162.e15. doi: 10.1016/j.cell.2016.07.025. PMID: 27565344 [cover illustration]

Doan RD, Bae BI, Cubelos B, Chang C, Hossain AA, Al-Saad S, Mukaddes NM, Oner O, Al-Saffar M, Balkhy S, Gascon GG, The Homozygosity Mapping Consortium for Autism, Nieto M, Walsh CA. Mutations in Human Accelerated Regions (HARs) are associated with abnormal social and cognitive behavior.
Cell 2016 Oct 6;167(2):341-354. PMID: 27667684

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