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EFFECTS OF FIBROBLAST GROWTH FACTOR RECEPTOR (FGFR) INHIBITOR, SU5402, ON CRANIOFACIAL DEVELOPMENT IN CHICKEN EMBRYOS

Ashley Rowan and Justin A Spenillo, Franklin & Marshall College

ABSTRACT

Fibroblast growth factor (FGF) signaling plays a signifigant role in embryonic development. Particularyl, FGFs are implicated in mediating epithelial-mesenchymal interactions by means of regulating cell proliferation and differentiation. FGF signaling is required for for limb bud and craniofacial development among other develpmental processes (Min et al. 1998; Ochuchi et al. 1997; Iseki et al. 1999; Crossley et al. 1996; Sheqetani et al. 2000). It has also been demonstrated that sonic hedgehog (SHH) signaling is necessary for proper limb bud and craniofacial development. shh null mutants exhibit impaired limb bud outgrowth, absence of digits, cyclopia and other caniofacial malformations (Chiang et al. 1996). It has been demonstrated that fgf and shh expression levels are corelated in a manner indicative of a regulatory relationship in the in developmental systems includig the limb (Gilbert 2000). To study the effect of fgf signaling on early chicken development, we interfered with FGF signaling by treating embryos with SU5402 (Calbiochem), a FGF receptor inhibitor. We observed craniofacial deformities and delayed maturation in embryos treated with SU5402. this indicates that FGF signaling is required for cranifacial formation and, more generally, development. Since FGFs are often involved in regulating shh, we processed SU5402 treated embryos with DIG-labled shh riboprobes. In situ hybridization revealed that when FGF signaling is perturbed, shh is upregulated throughout the embryo.

PURPOSE: The objective of this experiment is to study the effect of SU5402, a FGFR inhibitor, on early chicken development and the subsequent effects on shh expression.

INTRODUCTION
The development of a fertilized egg into a multicellular organism comprised of many specific tissues and structures requires a precisely coordinated repertoire of cellular processes. Cell-cell interactions are essential to the formation of an organism, and the proper genetic signals must be properly orchestrated to mediate these interactions. Paracrine factors are soluble proteins that travel short distances to induce changes in nearby cells. Mutations in genes coding for these signaling molecules can result in developmental abnormalities and in some, cases mutations are lethal.
Fibroblast growth factors(FGFs) comprise a family of paracrine factors that are involved in many developmental processes including craniofacial development, limb bud development, blood formation, and lung morphogenesis. FGFs transduce

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Last Modified: 2 August 2001

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