The Bmp gradient of the zebrafish gastrula guides migrating lateral cells by regulating cell-cell adhesion.
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.
von der Hardt
Sophia
S
Max-Planck Institute of Immunobiology, D-79108 Freiburg, Germany.
Bakkers
Jeroen
J
Inbal
Adi
A
Carvalho
Lara
L
Solnica-Krezel
Lilianna
L
Heisenberg
Carl-Philipp
CP
Hammerschmidt
Matthias
M
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*
D019485:Bone Morphogenetic Proteins; D015820:Cadherins; D002614:Chelating Agents; D029961:Zebrafish Proteins; D002118:Calcium