Biologie cellulaire et du développement
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Misguided Migration of C Cell Precursors to Extra-Thyroidal Locations Related to Defective Pharyngeal Pouch Development in Shh Deficient Mice

Jessica Westerlund, Louise Andersson, Therese Carlsson, Henrik Fagman and Mikael Nilsson

A possible role of sonic hedgehog (Shh) in recruitment of C cell precursors to the Ultimobranchial Body (UB) and embryonic thyroid was investigated in Shh-/- mice. Nkx2.1 and Foxa2 co-expression distinguished UB originating in the fourth pharyngeal pouch from other derivatives of pharyngeal endoderm. In mutants UB formed a single structure that failed to bud and instead of fusing with the midline thyroid primordium adhered to the thymic rudiments. Mature C cells appeared in the UB remnant and ectopically in the thymic parenchyma, foregut endoderm and trachea. Thyroid did not contain C cells except minute numbers close to the tracheal interface. Tracing progeny in Shh-CRE/Rosa26R mice showed the vast majority of both UB and thyroid progenitors derived from Shh negative endoderm, but Shh expressing cells appeared in both thyroid primordia before fusion of the two. The findings indicate that Shh determines the endoderm territory for C cell differentiation and guides the migration of C cell precursors into the thyroid, presumably by regulating the separation of glandular domains in the pharyngeal pouch endoderm. A cell-autonomous role of Shh in thyroid morphogenesis is suggested.