New perspectives on the role of the fibroblast growth factor family in amphibian development

Abstract

It has been known for several years that the fibroblast growth factors (FGFs) have potent mesoderm-inducing activity. As a result they have been considered good candidates for one of the endogenous vegetally localized mesoderm-inducing signals in the amphibian Xenopus laevis. In this review the properties of the FGFs and their expression patterns in Xenopus are described. Recent work is discussed which reveals a close link between FGF signalling and regulation of the Xenopus brachyury (Xbra) gene. These data are used to build a model of FGF function which is quite different from what was originally conceived. Present evidence supports the view that during blastula stages the FGFs do not act as vegetally localized inducing signals. Instead, they are required in the animal hemisphere as competence factors, which provide a low level stimulation of the tyrosine kinase signal transduction pathway. FGF activity is necessary for the full range of responses to the vegetal inducing signals, including the activation of Xbra transcription in the marginal zone of the late blastula. Xbra is able to activate the zygotic transcription of eFGF, which suggests that there is a period of autocatalytic activation of eFGF and Xbra transcription within the forming mesoderm of the marginal zone. FGF activity continues to be required to maintain the expression of a sub-set of mesodermal genes, including Xbra, in the blastopore region and possibly also in the notochord through gastrula and neurula stages. In addition a role for the FGFs in anteroposterior specification and development of the myogenic lineages is discussed.

Lin28 proteins are required for germ layer specification in Xenopus

“…Current models suggest that FGFs are not the primary signals for mesoderm specification in amphibians, but are secondary signals produced in the nascent mesoderm in response to the primary signals, such as nodal and activin (Isaacs et al, 1994; SchulteMerker and Smith, 1995;Isaacs, 1997). We therefore investigated whether lin28 knockdown also interferes with the ability of activin to induce mesoderm and gastrulation-like elongation in animal cap explants.…”

“…However, lin28 knockdown greatly inhibits the formation of fluid-filled vesicles and the differentiation of mesoderm following culture in the presence of FGF (Fig. 4A,B), indicating that lin28 function is required for animal caps to respond appropriately to FGF signalling.Current models suggest that FGFs are not the primary signals for mesoderm specification in amphibians, but are secondary signals produced in the nascent mesoderm in response to the primary signals, such as nodal and activin (Isaacs et al, 1994; SchulteMerker and Smith, 1995;Isaacs, 1997). We therefore investigated whether lin28 knockdown also interferes with the ability of activin to induce mesoderm and gastrulation-like elongation in animal cap explants.…”

The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer.

“…This results in an orchestrated set of morphogenic movements and differentiation to generate specific sets of cell lineages (Beddington & Robertson 1999, Fraser & Harland 2000 (Kimelman et al 1992, Beddington & Smith 1993, Beddington & Robertson 1999, Vogel & Gerster 1999, Fraser & Harland 2000, Thisse et al 2000. Members of the TGFβ (nodal, activin and bone morphogenic proteins (BMPs)), Wnt, Hedgehog (Sonic Hedgehog (Shh)) and FGF (fgf-4 and fgf-8) families are important in controlling positional information, differentiation, patterning and cell movements during early embryonic development in vertebrates (Kimelman et al 1992, Beddington & Smith 1993, Cornell & Kimelman 1994, Ungar et al 1995, Furthauer et al 1997, Isaacs 1997, McGrew et al 1997, Rossant et al 1997, Burdsal et al 1998, Dale & Jones 1999, Kofron et al 1999, McDowell & Gurdon 1999, Miller et al 1999, Vogel & Gerster 1999, Wicking et al 1999, Christian 2000, Gritsman et al 2000, Nishita et al 2000, Schier & Shen 2000, Thisse et al 2000. Antagonistic binding proteins such as follistatin, noggin, chordin, antivin and cerberus for specific members within the TGFβ family and antagonists for the Wnt family such as cerberus, frizzled-related protein (FRP) and dickkopf-1 (dkk-1) are also expressed during early embryogenesis (Piccolo et al 1996, Capdevila & Belmonte 1999, Meno et al 1999, Smith 1999, Thisse & Thisse 1999, Belo ...…”

“…These events are quite analogous to events which occur during the invasive stages of tumor cell metastasis where tumor epithelial cells become motile and assume more mesenchymal characteristics (Guarino et al 1999, Thiery & Chopin 1999. Differentiation of posterior epiblast cells into mesoderm cells and their migration away from the primitive streak are controlled by an integrative and synergistic effect of overlapping extracellular signals such as activin, BMP-4, nodal, wnt-8 and fgf-8, in conjunction with the appropriate spatial expression of receptors and intracellular signaling proteins for these growth factors and morphogens (Table 3) (Kimelman et al 1992, Beddington & Smith 1993, Cornell & Kimelman 1994, Ungar et al 1995, Furthauer et al 1997, Isaacs 1997, McGrew et al 1997, Rossant et al 1997, Dale & Jones 1999, Kofron et al 1999, McDowell & Gurdon 1999, Vogel & Gerster 1999, Schier & Shen 2000. Disruption of any of these signaling pathways can impair gastrulation and is therefore embryonically lethal (Deng et al 1994, Yamaguchi et al 1994, Ciruna et al 1997, Gu et al 1998, Sirard et al 1998, Wacker et al 1998, Waldrip et al 1998, Heyer et al 1999, Song et al 1999, Sun et al 1999.…”

Identification and characterization of an intracellular protein complex that binds fibroblast growth factor-2 in bovine brain

“…Fibroblast growth factor-2 (FGF-2) is a member of the FGF family, which currently includes 18 other proteins ( [1][2][3] and references therein). FGF-2 is a pleiotropic factor mediating various biological activities, such as proliferation and differentiation of a wide range of cells, wound healing and angiogenesis [3,4].…”