FRS2α is required for the separation, migration, and survival of pharyngeal-endoderm derived organs including thyroid, ultimobranchial body, parathyroid, and thymus

Abstract

The docking protein FRS2α plays an important role in fibroblast growth factor (FGF)-induced intracellular signal transduction by linking FGF receptors (FGFRs) to a variety of intracellular signaling pathways. In FRS2α2F/2F mutant mice at embryonic day (E)18.5, in which the Shp2-binding sites of FRS2α were disrupted, the thyroid glands were aplastic or hypoplastic. C cells were absent or present in low numbers and rarely formed a compact mass of cells. Parathyroid glands were mostly connected to thymus tissues. At E10.5, the formations of pharyngeal pouches and thyroid primordium were normally initiated in the mutant mice. At E11.5 to E12.5, the thyroid primordium of wild-type embryos was located close to the aortic sac, and the epithelial buds of pharyngeal-derived organs, including the parathyroid gland, thymus and ultimobranchial body, were separated from the epithelium and began to migrate to their final destinations. In the FRS2α2F/2F mutants, however, the thyroid primordium became hypoplastic and the pharyngeal-derived organ primordia remained affiliated with the pharyngeal epithelium. At these stages, organ-specific differentiation markers (i.e., Nkx2-1/TTF1 for the thyroid lobe and ultimobranchial body; Pax8 for the thyroid lobe; parathormone (PTH), chromogranin A, P75NTR, and S100 protein for the parathyroid gland; and p63 for the thymus) were normally expressed in the mutant tissues. Thus, the separation, migration, and survival of the pharyngeal organs were impaired in the FRS2α2F/2F mutants. © 2009 Wiley-Liss, Inc.