Premium
Distinct roles for N‐Cadherin linked c‐Src and fyn kinases in lens development
Author(s) -
Leonard Michelle,
Zhang Liping,
Bleaken Brigid M.,
Menko A. Sue
Publication year - 2013
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.23935
Subject(s) - fyn , biology , microbiology and biotechnology , proto oncogene tyrosine protein kinase src , morphogenesis , src family kinase , cadherin , gene knockdown , cellular differentiation , lens (geology) , tyrosine kinase , tyrosine protein kinase csk , signal transduction , cell , sh3 domain , cell culture , genetics , gene , paleontology
Background: Src family tyrosine kinases (SFKs) are often coincidently expressed but few studies have dissected their individual functions in the same cell during development. Using the classical embryonic lens as our model, we investigated SFK signaling in the regulation of both differentiation initiation and morphogenesis, and the distinct functions of c‐Src and Fyn in these processes. Results: Blocking SFK activity with the highly specific inhibitor PP1 induced initiation of the lens differentiation program but blocked lens fiber cell elongation and organization into mini lens‐like structures called lentoids. These dichotomous roles for SFK signaling were discovered to reflect distinct functions of c‐Src and Fyn and their differentiation‐state‐specific recruitment to and action at N‐cadherin junctions. c‐Src was highly associated with the nascent N‐cadherin junctions of undifferentiated lens epithelial cells. Its siRNA knockdown promoted N‐cadherin junctional maturation, blocked proliferation, and induced lens cell differentiation. In contrast, Fyn was recruited to mature N‐cadherin junctions of differentiating lens cells and siRNA knockdown suppressed differentiation‐specific gene expression and blocked morphogenesis. Conclusions: Through inhibition of N‐cadherin junction maturation, c‐Src promotes lens epithelial cell proliferation and the maintenance of the lens epithelial cell undifferentiated state, while Fyn, signaling downstream of mature N‐cadherin junctions, promotes lens fiber cell morphogenesis. Developmental Dynamics 242:469–474, 2013 . © 2013 Wiley Periodicals, Inc.