title: Segmental assembly of fibronectin matrix requires rap1b and integrin α5.
abstract: BACKGROUND
  During segmentation of the zebrafish embryo, inside-out signaling activates Integrin α5, which is necessary for somite border morphogenesis. The direct activator of Integrin α5 during this process is unknown. One candidate is Rap1b, a small monomeric GTPase implicated in Integrin activation in the immune system.
  
  
  RESULTS
  Knockdown of rap1b, or overexpression of a dominant negative rap1b, causes a mild axis elongation defect in zebrafish. However, disruption of rap1b function in integrin α5(-/-) mutants results in a strong reduction in Fibronectin (FN) matrix assembly in the paraxial mesoderm and a failure in somite border morphogenesis along the entire anterior-posterior axis. Somite patterning appears unaffected, as her1 oscillations are maintained in single and double morphants/mutants, but somite polarity is gradually lost in itgα5(-/-) ; rap1b MO embryos.
  
  
  CONCLUSIONS
  In itgα5(-) (/) (-) mutants, rap1b is required for proper somite border morphogenesis in zebrafish. The loss of somite borders is not a result of aberrant segmental patterning. Rather, somite boundary formation initiates but is not completed, due to the failure to assemble FN matrix along the nascent boundary. We propose a model in which Rap1b activates Integrin/Fibronectin receptors as part of an "inside-out" signaling pathway that promotes Integrin binding to FN, FN matrix assembly, and subsequent stabilization of morphological somite boundaries.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Lackner
authors.forename: Jamie
authors.initials: J
authors.lastname: Schwendinger-Schreck
authors.forename: Dörthe
authors.initials: D
authors.lastname: Jülich
authors.forename: Scott A
authors.initials: SA
authors.lastname: Holley
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D002970:Cleavage Stage, Ovum / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009024:Morphogenesis / Q000502:physiology; D060172:Morpholinos / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D019170:Somites / Q000196:embryology; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*; D020668:rap GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D039482:Integrin alpha5; D060172:Morpholinos; D029961:Zebrafish Proteins; C582061:Rap1b protein, zebrafish; D020668:rap GTP-Binding Proteins