Cellular and molecular events on the development of mammalian thyroid C cells

Thyroid C cells synthesize and secrete calcitonin, a serum calcium-lowering hormone. This review provides our current understanding of mammalian thyroid C cells from the molecular and morphological perspectives. Several transcription factors and signaling molecules involved in the development of C cells have been identified, and genes expressed in the pharyngeal pouch endoderm, neural crest-derived mesenchyme in the pharyngeal arches, and ultimobranchial body play critical roles for the development of C cells. It has been generally accepted, without much-supporting evidence, that mammalian C cells, as well as the avian cells, are derived from the neural crest. However, by fate mapping of neural crest cells in both Wnt1-Cre/R26R and Connexin(Cxn)43-lacZ transgenic mice, we showed that neural crest cells colonize neither the fourth pharyngeal pouch nor the ultimobranchial body. E-cadherin, an epithelial cell marker, is expressed in thyroid C cells and their precursors, the fourth pharyngeal pouch and ultimobranchial body. Furthermore, E-cadherin is colocalized with calcitonin in C cells. Recently, lineage tracing in Sox17-2A-iCre/R26R mice has clarified that the pharyngeal endoderm-derived cells give rise to C cells. Together, these findings indicate that mouse thyroid C cells are endodermal in origin.