Abstract
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.
Highlights
The thyroid contains two endocrine cell types, the follicular epithelial cells and the parafollicular C cells, which have different embryonic origins
This showed that neither the Ultimobranchial Bodies (UB) nor mature C cells expressed the R26 reporter gene that is known to be indelibly co-activated in all NC cells (NCC) progeny once by recombination with Wnt1 is expressed in the dorsal neural tube destined to a Neural Crest (NC) fate-Cre, which indelibly marks the progeny of NCC [7]
The sonic hedgehog (Shh) knockout mouse is previously known to exhibit a thyroid phenotype consisting of a hypoplastic gland and ectopic thyroid tissue located in the tracheal wall [17]
Summary
The thyroid contains two endocrine cell types, the follicular epithelial cells and the parafollicular C cells, which have different embryonic origins. Thyroid follicular progenitors are specified in the anterior foregut and form a midline primordium that buds from the pharyngeal endoderm and descends to the final position of the gland close to the larynx and proximal trachea. A neuroectodermal origin of thyroid C cells was, recently challenged by data obtained from genetic fate mapping studies in mice [6]. This showed that neither the UB nor mature C cells expressed the R26 reporter gene that is known to be indelibly co-activated in all NCC progeny once by recombination with Wnt is expressed in the dorsal neural tube destined to a NC fate-Cre, which indelibly marks the progeny of NCC [7]. The embryonic origin of mammalian C cells remains to be established
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