Villacorte M., Delmarcelle A.S., Lernoux M., Bouquet M., Lemoine P., Bolsée J., Umans L., de Sousa Lopes S.C., Van Der Smissen P., Sasaki T., Bommer G., Henriet P., Refetoff S., Lemaigre F.P., Zwijsen A., Courtoy P.J., Pierreux C.E.
Thyroid follicles, the functional units of the thyroid gland, are delineated by a monolayer of thyrocytes resting on a continuous basement membrane. Here the authors show that assembly of the epithelial basement membrane is critical for folliculogenesis and is controlled by endothelial cell invasion and by BMP-Smad signaling in thyrocytes. Thyroid-specific double Smad1 and Smad5 knockout mice (Smad1/5dKO) displayed growth retardation, hypothyroidism, and defective follicular architecture. Interestingly, both VegfaKOand Smad1/5dKOthyroids displayed impaired basement membrane assembly. Furthermore, conditioned medium (CM) from embryonic endothelial progenitor cells (eEPC) rescued the folliculogenic defects of bothSmad1/5dKOand VegfaKOthyroids. Laminin-111, abundantly released by eEPC into CM, was critically required for folliculogenesis. Thus, epithelial Smad signaling and endothelial cell invasion promote folliculogenesis via the assembly of the basement membrane.