Expression of the Epithelial Marker E-Cadherin by Thyroid C Cells and Their Precursors During Murine Development

Abstract

S U M M A R Y Studies of chick-quail chimeras have reported that avian ultimobranchial C cells originate from the neural crest. It has consequently been assumed, without much supporting evidence, that mammalian thyroid C cells also originate from the neural crest. To test this notion, we employed both Connexin43-lacZ and Wnt1-Cre/R26R transgenic mice, because their neural crest cells can be marked. We also examined the immunohistochemical expression of a number of markers that identify migratory or postmigratory neural crest cells, namely, TuJ1, neurofilament 160, nestin, P75NTR, and Sox10. Moreover, we examined the expression of E-cadherin, an epithelial cell marker. At embryonic day (E)10.5, the neural crest cells densely populated the pharyngeal arches but were not distributed in the pharyngeal pouches, including the fourth pouch. At E11.5, the ultimobranchial rudiment formed from the fourth pouch and was located close to the fourth arch artery. At E13.0, this organ came into contact with the thyroid lobe, and at E13.5, it fused with this lobe. However, the ultimobranchial body was not colonized by neural crest-derived cells at any of these developmental stages. Instead, all ultimobranchial cells, as well as the epithelium of the fourth pharyngeal pouch, were intensely immunoreactive for E-cadherin. Furthermore, confocal microscopy of newborn mouse thyroid glands revealed colocalization of calcitonin and E-cadherin in the C cells. The cells, however, were not marked in the Wnt-Cre/R26R mice. These results indicated that murine thyroid C cells are derived from the endodermal epithelial cells of the fourth pharyngeal pouch and do not originate from neural crest cells.

Expression of Islet1 in thyroid development related to budding, migration, and fusion of primordia

“…According to the classic quail-chick chimera experiments by Le Dourain and co-workers more than thirty years ago (Le Douarin and Le Lievre, 1970;Polak et al, 1974) the developmental source of C-cells is believed to be the neural crest that contributes with the main cellular component of the avian ultimobranchial body. However, recent genetic fate mapping studies on the progeny of Wnt1-expressing neural crest failed to demonstrate a neuroectodermal origin of mouse C-cells (Kameda et al, 2007a). Although it cannot be excluded that neural crest progenitors routed to the pharyngeal arches acquire Isl1 expression (this has been shown for neural crest cells differentiating into dorsal root and sympathetic ganglia; Ericson et al, 1992), the present data are compatible with the hypothesis that the foregut endoderm gives rise to both thyroid endocrine cell types in the mouse.…”

Morphogenesis of the thyroid gland

“…In contrast, during development the mouse UB is not in the immediate vicinity of ganglia or nerve bundles and there is no evidence of such a contribution to thyroid C-cells (Kameda et al, 2007a).…”

“…The most compelling evidence favouring the hypothesis that C-cells of the mouse thyroid are likely not of NC origin comes from a recent lineage tracing experiment, using the Wnt1-Cre driver that faithfully marks the migrating NC population and its descendants (Jiang et al, 2000). It was demonstrated that Wnt1-expressing NCC cells did not show up in the UB at any developmental stage, nor was the distribution pattern overlapping with the calcitonin-positive cells in the mature gland (Kameda et al, 2007a). The endoderm of the fourth pharyngeal pouch therefore is the most obvious candidate origin of C-cell precursors in the mouse.…”

“…Indeed, recent fate mapping of NCC and their progeny using the Wnt1-Cre driver has revealed that the developing thyroid is heavily invested by NC derived ectomesenchyme (Jiang et al, 2000). Also the mesenchyme of the mature gland is at least partly of NC origin as evident from chimeric quail and chick embryos (Le Lievre and Le Douarin, 1975) and Wnt1-Cre based fate mapping (Kameda et al, 2007a). Considering the profound impact defective NCC migration has on the gross pharyngeal anatomy it is likely that the thyroid phenotype is secondary to other morphogenetic events.…”

“…The prevailing concept of a NC origin of C-cells therefore rests on other lines of evidence, one is more conceptual and derived by assuming a common developmental origin of all neuroendocrine cells, the other is based on data obtained from xenotransplants of embryonic tissues. As the embryonic source of C-cells at least in higher vertebrates has recently been challenged (Kameda et al, 2007a), it is relevant to highlight some of the historic background.…”