BBS Faculty Member - Xianhua Piao

Xianhua Piao

Department of Medicine

Boston Children's Hospital
Enders Building, Room 961.2
300 Longwood Avenue
Boston, MA 02115
Tel: 617-919-2357
Fax: 617-730-0260
Visit my lab page here.

The research in the Piao lab is directed at understanding how cells communicate with their microenvironment (extracellular matrix) during normal brain development as well as in the case of neurological diseases. In particular, we are investigating signaling mechanisms employed by a member of the adhesion G protein-coupled receptor family, GPR56. While characterizing a newly defined human brain malformation, we discovered that GPR56 is the disease-causing gene. When GPR56 is mutated, the formation of the cerebral cortex is severely disrupted, particularly in the frontal cortex.

There are two major lines of ongoing research in the lab. The first is to identify molecular components of GPR56 signaling pathways and the mechanisms by which GPR56 pathways are activated and governed during brain development and malformation. To this end, we discovered that collagen III is the ligand of GPR56 in the developing brain and that the binding of collagen III to GPR56 activates RhoA pathway by coupling to Gα12/13.This finding was particularly interesting, as collagen III is a constituent of the extracellular matrix that covers the developing cortex known as the pial basement membrane. The fact that the ligand of GPR56 was in the pial basement membrane provided strong evidence that GPR56-expressing migrating cells must be actively communicating with the basement membrane in order to ensure proper brain development.

The second major line of ongoing research is to determine which cells are chiefly responsible for this interaction. We found that the first-born neurons, known as preplate neurons, expressed GPR56 most strongly in the frontal cortex – the same region of the cortex that is most devastated when GPR56 is mutated. Although the molecular mechanisms underlying the function of these preplate neurons remain largely unknown, our data indicates that GPR56 must play an important role in their function. In the next phase of our research, we will continue to study how GPR56 mediates the interaction between the preplate neurons and pial basement membrane, particularly in an attempt to elucidate how they work together to define the boundary between the neocortex and the pial basement membrane while providing a framework for the developing brain.

Last Update: 8/22/2013


Li S, Jin Z, Koirala S, Bu L, Xu L, Hynes RO, Walsh CA, Corfas G, and Piao X. GPR56 Regulates Pial Basement Membrane Integrity and Cortical Lamination. The Journal of Neuroscience 2008, 28(22):5817-26

Luo R, Jeong SJ, Jin Z, Strokes N, Li S,
Piao X. G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination. Proceedings of the National Academy of Sciences of the United States of America 2011, 108(31):12925-30. PMCID: PMC3150909

Jeong S-J, Li S, Luo R, Strokes N,
Piao X. Loss of Col3a1, the Gene for Ehlers-Danlos Syndrome Type IV, Results in Neocortical Dyslamination. PLoS ONE 2012, 7(1): e29767. PMCID: PMC3250483

Jeong SJ, Luo R, Li S, Strokes N,
Piao X. Characterization of G Protein-Coupled Receptor 56 Protein Expression in the Mouse Developing Neocortex. The Journal of Comparative Neurology. 2012 Feb 20. doi: 10.1002/cne.23076.

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