title: Gβ1 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 Gβ1 is essential for proper pLLP migration. Although both Gβ1 and Gβ4 are expressed in the pLLP and NMs, depletion of Gβ1 but not Gβ4 resulted in an arrest of pLLP migration. In embryos deficient for Gβ1, 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, Gβ1 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 Gβ1, Cxcr4b or Cxcl12a do not. Finally, synergy experiments revealed that Gβ1 and Cxcr4b interact genetically in regulating pLLP migration. Collectively, our data indicate that Gβ1 controls migration of the pLLP, likely by acting downstream of the Cxcl12a/Cxcr4b signaling. This study also provides compelling evidence for functional specificity among Gβ isoforms in vivo.
authors.affiliation: Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, USA.
authors.forename: Ding
authors.initials: D
authors.lastname: Ye
authors.affiliation: Department of Anatomy and Neurobiology, University of Puerto Rico, USA.
authors.forename: Martine
authors.initials: M
authors.lastname: Behra
authors.affiliation: Genome Technology Branch, NHGRI/NIH, Bethesda, MD, USA.
authors.forename: Shawn
authors.initials: S
authors.lastname: Burgess
authors.affiliation: Department of Pharmacology, Carver College of Medicine, University of Iowa, USA.
authors.forename: Songhai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, USA. Electronic address: fang-lin@uiowa.edu.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D017931:DNA Primers; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D053403:Lateral Line System / Q000166:cytology / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: C471276:CXCR4b protein, zebrafish; D054377:Chemokine CXCL12; D017931:DNA Primers; D019718:Receptors, CXCR4; D029961:Zebrafish Proteins; C579453:cxcl12a protein, zebrafish; D020962:Heterotrimeric GTP-Binding Proteins
keywords: Cell migration; G protein; Gβ1; Posterior lateral line primordium; Zebrafish