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Cebra-Thomas Lab

The role of signaling molecules in craniofacial development

Many organs develop through inductive interactions between adjacent tissue layers mediated by signaling molecules including sonic hedgehog (SHH) and members of the fibroblast growth factor (FGF) family. SHH and FGFs have been shown to be involved in a feedback loop during limb development (Niswander et al., 1994, Nature 371:609). As shh and fgfsare often expressed in adjacent tissue layers, such a signaling loop may be a general feature of organogenesis. Exposure of chick embryos to cyclopamine (a steriodal alkaloid) inhibits the response of target cells to SHH signaling, and induces craniofacial malformations including fusion of optic vesicles, nasal placodes, and maxillary and mandibular arches (Cooper et al., 1998, Science 280:1603). To determine if these malformations result from loss of inductive signals, we treated chick embryos with cyclopamine and looked for changes in gene expression. Primitive streak-stage embryos were treated with 5 mg of cyclopamine for 3 days, fixed and subjected to in situ hybidization. Cyclopamine treatment results in a marked reduction of fgf8expression in the branchial arches and frontonasal process, and of shhin the frontonasal process, nasal placodes and branchial arches. This suggests that SHH signaling is required for the initiation or mantenance of fgf8epression, and FGF8 signaling in turn is required to maintain shhexpression during craniofacial development.

@Cebra-Thomas, 2001

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