G?1 controls collective cell migration by regulating the protrusive activity of leader cells in the posterior lateral line primordium.

ABSTRACT: Collective cell migration is critical for normal development, tissue repair and cancer metastasis. Migration of the posterior lateral line primordium (pLLP) generates the zebrafish sensory organs (neuromasts, NMs). This migration is promoted by the leader cells at the leading edge of the pLLP, which express the G protein-coupled chemokine receptor Cxcr4b and respond to the chemokine Cxcl12a. However, the mechanism by which Cxc112a/Cxcr4b signaling regulates pLLP migration remains unclear. Here we report that signal transduction by the heterotrimeric G protein subunit G?1 is essential for proper pLLP migration. Although both G?1 and G?4 are expressed in the pLLP and NMs, depletion of G?1 but not G?4 resulted in an arrest of pLLP migration. In embryos deficient for G?1, the pLLP cells migrated in an uncoordinated fashion and were unable to extend protrusions at the leading front, phenocopying those in embryos deficient for Cxcl12a or Cxcr4b. A transplantation assay showed that, like Cxcr4b, G?1 is required only in the leader cells of the pLLP. Analysis of F-actin dynamics in the pLLP revealed that whereas wild-type leader cells display extensive actin polymerization in the direction of pLLP migration, counterparts defective for G?1, Cxcr4b or Cxcl12a do not. Finally, synergy experiments revealed that G?1 and Cxcr4b interact genetically in regulating pLLP migration. Collectively, our data indicate that G?1 controls migration of the pLLP, likely by acting downstream of the Cxcl12a/Cxcr4b signaling. This study also provides compelling evidence for functional specificity among G? isoforms in vivo.

SUBMITTER: Xu H 

PROVIDER: S-EPMC4134875 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature