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

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-beta (TGF-beta) and fibroblast growth factor (FGF) ligand families seem to have critical roles in this process. 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.

Vertebrate Ctr1 coordinates morphogenesis and progenitor cell fate and regulates embryonic stem cell differentiation

“…Although FGF is not thought to function as a primary mesoderm inducer in vivo, exogenous FGF can induce mesoderm in ectodermal explants (27). The Xctr1-interacting protein, Laloo, is required for FGF-mediated mesoderm induction and induces expression of the early panmesodermal gene Xbrachyury (Xbra) in gastrula-stage animal cap explants (9). Xctr1 RNA injection alone does not induce Xbra expression in this assay ( Fig.…”

“…A dramatic example of this phenomenon occurs during early vertebrate embryogenesis, when fibroblast growth factor (FGF) mediates multiple developmental processes. During mesoderm induction, FGF triggers activation of a Ras-MAPK cascade (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). In contrast, subsequent morphogenesis of the dorsal mesoderm is regulated by a noncanonical FGF pathway that is independent of Ras-MAPK signaling and may involve stimulation of Ca 2ϩ release and/or activation of phospholipase C␥ (PLC␥) (13,14).…”

“…All other primer sequences are as described (40). Whole-mount antibody staining and in situ hybridization was performed as described (9). The 12/101 and Xen-1 antibodies (Developmental Studies Hybridoma Bank, Iowa City, IA) were used at a 1:1 dilution for somite and neural staining, respectively.…”

Fibroblast Growth Factor-2-induced Signaling through Lipid Raft-associated Fibroblast Growth Factor Receptor Substrate 2 (FRS2)

“…Studies on Xenopus laevis have demonstrated that Laloo, a novel member of the Src family of tyrosine kinases, is required for mesoderm induction in response to FGF (13). The cooperation of FRS2 and Laloo in this pathway is suggested by the observed association of FRS2 with Laloo (14,15).…”

Oncogenic Met receptor induces ectopic structures in Xenopus embryos

“…An activated FGF receptor 1, like several FGF signaling pathway elements (Pownall et al, 1996;Tada et al, 1997;Weinstein et al, 1998;Brewster et al, 2000;Hama et al, 2001;Park et al, 2004), induces ectopic structures. Several members of the Met signaling pathway are also common to the FGF signaling pathway (Furge et al, 2000; Powers et al, 2000), including Ras/Raf/Mek/MAPK.…”