a src-tks5 pathway is required for neural crest cell migration during embryonic developmentsrc-tks5途径需要在胚胎发育神经嵴细胞的迁移.pdfVIP

A Src-Tks5 Pathway Is Required for Neural Crest Cell Migration during Embryonic Development 1 ˜ 1. 1.¤a 2 3¤b Danielle A. Murphy , Begona Diaz , Paul A. Bromann , Jeff H. Tsai , Yasuhiko Kawakami , Jochen 1 4 ´ 2 1 Maurer , Rodney A. Stewart , Juan Carlos Izpisua-Belmonte , Sara A. Courtneidge * 1 Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America, 2 Department of Pharmacology, University of California San Diego, La Jolla, California, United States of America, 3 Salk Institute for Biological Studies, La Jolla, California, United States of America, 4 Huntsman Cancer Institute, Salt Lake City, Utah, United States of America Abstract In the adult organism, cell migration is required for physiological processes such as angiogenesis and immune surveillance, as well as pathological events such as tumor metastasis. The adaptor protein and Src substrate Tks5 is necessary for cancer cell migration through extracellular matrix in vitro and tumorigenicity in vivo. However, a role for Tks5 during embryonic development, where cell migration is essential, has not been examined. We used morpholinos to reduce Tks5 expression in zebrafish embryos, and observed developmental defects, most prominently in neural crest-derived tissues such as craniofacial structures and pigmentation. The Tks5 morphant phenotype was rescued by expression of mammalian Tks5, but not by a variant of Tks5 in which the Src phosphorylation sites have been mutated. We further evaluated the role of Tks5 in neural crest cells and neural crest