Abstract
The thyroid develops from distinct regions in the foregut endoderm, the midline and lateral primordia. To date no cell-autonomous factor responsible for the early specification of thyroid progenitor cells has been uncovered. Hence, the events leading to recruitment of a subset of endoderm cells to a thyroid precursor fate remain to be characterized. The morphogen Sonic hedgehog (Shh) is preferentially expressed in the ventral foregut endoderm, but is excluded from the thyroid placode populated by Tif1/Nkx2.1 (formerly named TTF-1) expressing cells. Yet, Shh null mice present thyroid developmental defects. To get further insight into the role of Shh in thyroid development, we investigated whether thyroid precursor cells and their progeny express Shh before or after the bud stages by a fate mapping strategy using Shh-Cre and the Rosa26 conditional reporter (R26R) mouse lines. Double heterozygous mutants were found to express Shh in the expected embryonic tissues: anterior endoderm, notochord, floor plate, presumptive trachea and oesophagus. In E9.5-12.5 embryos no Shh positive cells were observed in the budding or migrating midline thyroid anlage. However, a limited segment of the anterior portion of the ultimobranchial bodies evaginating from the fourth pharyngeal pouches were Shh positive. Such cells of Shh positive endoderm origin were found scattered throughout the thyroid parenchyma after the fusion of primordia at E13.5. This is the first fate mapping analysis of endoderm progenitors implicated in thyroid development. It shows that precursor cells of the follicular epithelium likely are recruited from a Shh-free zone in the primitive foregut endoderm, presumably lateral or dorsal to the midline thyroid placode. Shh expressing endoderm lineage cells enter the developing thyroid via the ultimobranchial bodies, suggesting a cell-autonomous role of Shh at some stage(s) of thyroid morphogenesis.