title: The Bmp gradient of the zebrafish gastrula guides migrating lateral cells by regulating cell-cell adhesion.
abstract: BACKGROUND
  Bone morphogenetic proteins (Bmps) are required for the specification of ventrolateral cell fates during embryonic dorsoventral patterning and for proper convergence and extension gastrulation movements, but the mechanisms underlying the latter role remained elusive.
  
  
  RESULTS
  Via bead implantations, we show that the Bmp gradient determines the direction of lateral mesodermal cell migration during dorsal convergence in the zebrafish gastrula. This effect is independent of its role during dorsoventral patterning and of noncanonical Wnt signaling. However, it requires Bmp signal transduction through Alk8 and Smad5 to negatively regulate Ca(2+)/Cadherin-dependent cell-cell adhesiveness. In vivo, converging mesodermal cells form lamellipodia that attach to adjacent cells. Bmp signaling diminishes the Cadherin-dependent stability of such contact points, thereby abrogating subsequent cell displacement during lamellipodial retraction.
  
  
  CONCLUSIONS
  We propose that the ventral-to-dorsal Bmp gradient has an instructive role to establish a reverse gradient of cell-cell adhesiveness, thereby defining different migratory zones and directing lamellipodia-driven cell migrations during dorsal convergence in lateral regions of the zebrafish gastrula.
authors.affiliation: Max-Planck Institute of Immunobiology, D-79108 Freiburg, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: von der Hardt
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bakkers
authors.forename: Adi
authors.initials: A
authors.lastname: Inbal
authors.forename: Lara
authors.initials: L
authors.lastname: Carvalho
authors.forename: Lilianna
authors.initials: L
authors.lastname: Solnica-Krezel
authors.forename: Carl-Philipp
authors.initials: CP
authors.lastname: Heisenberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Hammerschmidt
mesh_terms: D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D005775:Gastrula / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D015820:Cadherins; D002614:Chelating Agents; D029961:Zebrafish Proteins; D002118:Calcium