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FGF-mediated mesoderm induction involves the Src-family kinase Laloo

An Erratum to this article was published on 29 October 1998

Abstract

During embryogenesis, inductive interactions underlie the development of much of the body plan. In Xenopus laevis, factors secreted from the vegetal pole induce mesoderm in the adjacent marginal zone; members of both the transforming growth factor-β (TGF-β) and fibroblast growth factor (FGF) ligand families seem to have critical roles in this process1. Here we report the identification and characterization of laloo, a novel participant in the signal transduction cascade linking extracellular, mesoderm-inducing signals to the nucleus, where alteration of cell fate is driven by changes in gene expression. Overexpression of laloo, a member of the Src-related gene family, in Xenopus embryos gives rise to ectopic posterior structures that frequently contain axial tissue. Laloo induces mesoderm in Xenopus ectodermal explants; this induction is blocked by reagents that disrupt the FGF signalling pathway. Conversely, expression of a dominant-inhibitory Laloo mutant blocks mesoderm induction by FGF and causes severe posterior truncations in vivo. This work provides the first evidence that a Src-related kinase is involved in vertebrate mesoderm induction.

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Figure 1: Effects of injection of laloo into embryos.
Figure 2: laloo is a novel Src-related gene.
Figure 3: Ectopic Laloo induces mesoderm.
Figure 4: Y492F bypasses inhibition by XFD, and K259E inhibits the activity of mesoderm-inducing growth factors and normal development.

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Acknowledgements

We thank M. Whitman and E. Amaya for providing us with the Ras and XFD constructs, respectively; W. Harris for the 6F11 antibody; and members of the laboratory, P. Wilson and H. Hanafusa, for critical reading of the manuscript. F.C. received partial financial support from Programma Scambi Internazionali and Piano Bilaterale of CNR of Rome. A.H.-B. is a Merck and a McKnight scholar. This work was supported by NIH grant HD 32105-01 and by grants from the Klingenstein and Merck Foundations to A.H.-B.

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Correspondence to Ali Hemmati-Brivanlou.

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Weinstein, D., Marden, J., Carnevali, F. et al. FGF-mediated mesoderm induction involves the Src-family kinase Laloo. Nature 394, 904–908 (1998). https://doi.org/10.1038/29808

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