Glycolytic suppression of cell adhesion promotes thyroid morphogenesis in response to nutrition.

Organ morphogenesis relies on collective cellular behaviors. While intrinsic developmental programs governing cellular behaviors are well characterized, the effects of environmental and systemic factors on these behaviors remain poorly understood. Here, we investigate how nutritional availability modulates cellular behaviors during thyroid morphogenesis using Xenopus tadpoles as an in vivo model. RNA-seq analysis of thyroid regions from fed and unfed tadpoles shows that nutritional status alters gene expression profiles. We identify cell adhesion-related genes as key targets, with expression increased in unfed tadpoles and decreased in fed tadpoles. Immunostaining for E-cadherin supports the RNA-seq results, and functional inhibition of E-cadherin facilitates thyroid follicle formation. We further demonstrate that glycolytic activity reduces junctional E-cadherin accumulation in the thyroid, linking metabolism to the regulation of cell adhesion. Lastly, thyroid cells forming multi-luminal structures exhibit distinct apical-basal polarity, and these structures are enhanced by glycolytic activity and suppression of cell adhesion. These findings reveal a mechanism by which nutritional status remodels cellular properties underlying collective cellular behaviors during organ morphogenesis.