INTRODUCTION Fibroblast growth factors (FGFs) are small polypeptides that mediate embryonic induction in vertebrates. FGFs are important mediators of mesoderm induction in Xenopus and chick and of limb development in mouse and chick (Rappolee

Fibroblast growth factors (FGFs) are small polypeptides that mediate embryonic induction in vertebrates. FGFs are important mediators of mesoderm induction in Xenopus and chick and of limb development in mouse and chick (Rappolee and Werb, 1994; Niswander and Martin, 1992, 1993a,b; Vogel and Tickle, 1993). There are nine members of the FGF family (Hebert et al., 1990; Basilico and Moscatelli, 1992). In the present terminology, acidic FGF is FGF-1, basic FGF is FGF2, int-2 is FGF-3, Kaposi’s sarcoma-type FGF is FGF-4 and keratinocyte growth factor is FGF-7; the other members are FGF-5, FGF-6, FGF-8 and FGF-9 (Basilico and Moscatelli, 1992; Tanaka et al., 1992; Miyamoto et al., 1993). Several members of the FGF family can induce mesoderm and markers for posterior mesoderm in animal cap preparations from Xenopus embryos (Kimelman and Kirschner, 1987; Ruiz i Altaba and Melton, 1989; Paterno et al., 1989). In whole frog embryos, overexpression of FGF induces anterior and posterior mesoderm (Kimelman and Maas, 1992). Expression of a dominant negative FGF receptor disrupts posterior/ventral mesoderm and the expression of brachyury in Xenopus (Amaya et al., 1991, 1993). The role of FGF in early stages of mammalian development has not been well studied. Null mutants for FGF-3 have fewer vertebrae in the tail as well as other mutant phenotypes occurring later in development (Mansour et al., 1993). FGF-3, FGF-4 and FGF-5 are expressed at gastrulation (Hebert et al., 1990; Wilkinson et al., 1988; Niswander and Martin, 1992) in the day 7.0 post coitum (p.c.) mouse. At day 4.5 p.c., the inner cell mass (ICM) of the preimplantation mouse blastocyst contains FGF-4 mRNA (Niswander and Martin, 1992) but not FGF-2 (Rappolee et al., 1988). FGF-4 and FGF-3 are inversely regulated in embryonal carcinoma cells (Hebert et al., 1990; Velcich et al., 1989); that is, undifferentiated embryonal carcinoma stem cells express FGF-4 but not FGF-3, and differentiated cells (resembling parietal endoderm) express FGF3 but not FGF-4. FGF action is mediated through the cooperative interaction of a high-affinity FGF receptor and a requisite low-affinity FGF receptor, such as the heparan sulfate proteoglycan syndecan protein (Klagsbrun and Baird, 1991). There are four members of the family of high-affinity receptors for FGF (Dionne et al., 1990; Lee et al., 1989; Keegan et al., 1991; Partanen et al., 1991, 1992; Johnson et al., 1991). Expression of high-affinity FGF receptors during mouse development has 2259 Development 120, 2259-2269 (1994) Printed in Great Britain © The Company of Biologists Limited 1994