Mesoderm-independent regulation of gastrulation movements by the src tyrosine kinase in Xenopus embryo.
In vitro studies have demonstrated the involvement of Src kinases in several aspects of cell scattering, including cell dissociation and motility. We have therefore sought to explore their functions in the context of the whole organism. Loss-of-function microinjection studies indicate that the ubiquitous Src, Fyn, and Yes tyrosine kinases are specifically implicated in Xenopus gastrulation movements. Injection of mRNAs coding for dominant negative forms of the ubiquitous members of the Src family, namely Fyn, Src, and Yes, perturbs gastrulation movements, resulting in the inability to close the blastopore. Injection of mRNA coding for Csk, a natural inhibitor of Src kinase activity, produces the same phenotypic alterations. The ubiquitous Src kinases have redundant functions in gastrulation movements since overexpression of one member of the family can compensate for the inhibition of another. Interfering mutants of the Src family also inhibit activin-induced morphogenetic movements of animal cap explants isolated from injected embryos. In contrast, these mutants do not interfere with mesoderm induction, as inferred from the presence of mesoderm derivatives and from the expression of early mesodermal markers in injected embryos. In addition, Src kinase activity measured by an in vitro kinase assay is elevated in gastrulating embryos and in FGF- and activin-treated animal caps, confirming the implication of Src enzymatic activity during gastrulation. Altogether, our results demonstrate that Src kinases are essential components of the machinery that drives gastrulation movements independent of mesoderm induction and suggest that Src activity is primarily implicated in cellular movements that take place during the process of cell intercalation.
Denoyelle
M
M
UMR 146, Institut Curie Section de Recherche, Centre Universitaire Paris-Sud, Orsay, France.
Vallés
A M
AM
Lentz
D
D
Thiery
J P
JP
Boyer
B
B
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D005775:Gastrula / Q000502:physiology*; D005799:Genes, Dominant; D017403:In Situ Hybridization; D008648:Mesoderm; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis; D014981:Xenopus / Q000196:embryology; D018909:src Homology Domains; D019061:src-Family Kinases / Q000502:physiology*
D017931:DNA Primers; D012333:RNA, Messenger; D019061:src-Family Kinases