Gravin regulates mesodermal cell behavior changes required for axis elongation during zebrafish gastrulation.
Convergent extension of the mesoderm is the major driving force of vertebrate gastrulation. During this process, mesodermal cells move toward the future dorsal side of the embryo, then radically change behavior as they initiate extension of the body axis. How cells make this transition in behavior is unknown. We have identified the scaffolding protein and tumor suppressor Gravin as a key regulator of this process in zebrafish embryos. We show that Gravin is required for the conversion of mesodermal cells from a highly migratory behavior to the medio-laterally intercalative behavior required for body axis extension. In the absence of Gravin, paraxial mesodermal cells fail to shut down the protrusive activity mediated by the Rho/ROCK/Myosin II pathway, resulting in embryos with severe extension defects. We propose that Gravin functions as an essential scaffold for regulatory proteins that suppress the migratory behavior of the mesoderm during gastrulation, and suggest that this function also explains how Gravin inhibits invasive behaviors in metastatic cells.
Weiser
Douglas C
DC
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Pyati
Ujwal J
UJ
Kimelman
David
D
D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D018797:Cell Cycle Proteins; D002465:Cell Movement; D048430:Cell Shape; D005775:Gastrula / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000166:cytology; D008954:Models, Biological; D008969:Molecular Sequence Data; D024462:Myosin Type II / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D018797:Cell Cycle Proteins; D011506:Proteins; D012333:RNA, Messenger; D029961:Zebrafish Proteins; C532501:akap12b protein, zebrafish; D024462:Myosin Type II; D020742:rhoA GTP-Binding Protein