ror2 enhances polarity and directional migration of primordial germ cellsror2提高极性和原始生殖细胞的定向迁移.pdfVIP

Ror2 Enhances Polarity and Directional Migration of Primordial Germ Cells 1,2 . 1,2. 1,2 3,4 Diana J. Laird * , Svetlana Altshuler-Keylin , Michael D. Kissner , Xin Zhou , Kathryn V. Anderson3 1 Ob/Gyn Department, Center for Reproductive Sciences, University of California San Francisco, San Francisco, California, United States of America, 2 Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, United States of America, 3 Developmental Biology Program, Sloan Kettering Institute, New York, New York, United States of America, 4 Biochemistry and Structural Biology, Cell and Developmental Biology, and Molecular Biology Program, Weill Graduate School of Medical Sciences, Cornell University, New York, New York, United States of America Abstract The trafficking of primordial germ cells (PGCs) across multiple embryonic structures to the nascent gonads ensures the transmission of genetic information to the next generation through the gametes, yet our understanding of the mechanisms underlying PGC migration remains incomplete. Here we identify a role for the receptor tyrosine kinase-like protein Ror2 in PGC development. In a Ror2 mouse mutant we isolated in a genetic screen, PGC migration and survival are dysregulated, resulting in a diminished number of PGCs in the embryonic gonad. A similar phenotype in Wnt5a mutants suggests that Wnt5a acts as a ligand to Ror2 in PGCs, although we do not find evidence that WNT5A functions as a PGC chemoattractant. We show that cultured PGCs undergo polarization, elongation, and reorientation in response to the chemotactic factor SCF (secreted KitL), whereas Ror2 PGCs are deficient in these SCF-induced res