Noonan syndrome is associated with enhanced pERK activity, the repression of which can prevent craniofacial malformations.

ABSTRACT: A gain of function mutation in SHP2, a protein phosphatase encoded by PTPN11, causes Noonan syndrome (NS), which is characterized in part by developmental deficits in both the cardiac and skull fields. Previously, we found that expression of the mutated protein SHP2 Q79R in the heart led to a phenotypic presentation that mimicked some aspects of NS and that this was dependent upon activation of the ERK1/2 pathway. To understand the role that ERK1/2 signaling plays in skull development through signaling in the neural crest, we explored the consequences of Q79R expression in neural crest cells, which contribute to a subset of the bony and cartilaginous structures of the skull. Hyperactivation of ERK1/2 led to craniofacial defects that included smaller skull lengths, greater inner canthal dis

SUBMITTER: Nakamura T 

PROVIDER: S-EPMC2741269 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature