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Title Thyroid follicle development requires Smad1/5-and endothelial cell-dependent basement membrane assembly
Posted by Mylah Tabelin
Authors Mylah Villacorte, Anne-Sophie Delmarcelle, Manon Lernoux, Mahé Bouquet, Pascale Lemoine, Jennifer Bolsée, Lieve Umans, Susana Chuva de Sousa Lopes, Patrick Van Der Smissen, Takako Sasaki, Guido Bommer, Patrick Henriet, Samuel Refetoff, Frédéric P Lemaigre, An Zwijsen, Pierre J Courtoy, Christophe E Pierreux
Publication date 2016/6/1
Journal Development
Volume 143
Issue 11
Pages 1958-1970
Publisher The Company of Biologists
Abstract Thyroid follicles, the functional units of the thyroid gland, are delineated by a monolayer of thyrocytes resting on a continuous basement membrane. The developmental mechanisms of folliculogenesis, whereby follicles are formed by the reorganization of a non-structured mass of non-polarized epithelial cells, are largely unknown. Here we show that assembly of the epithelial basement membrane is crucial for folliculogenesis and is controlled by endothelial cell invasion and by BMP-Smad signaling in thyrocytes. Thyroid-specific Smad1 and Smad5 double-knockout (Smad1/5dKO) mice displayed growth retardation, hypothyroidism and defective follicular architecture. In Smad1/5dKO embryonic thyroids, epithelial cells remained associated in large clusters and formed small follicles. Although similar follicular defects are found in Vegfa knockout (VegfaKO) thyroids, Smad1/5dKO thyroids had normal endothelial cell density yet impaired endothelial differentiation. Interestingly, both VegfaKO and Smad1/5dKO thyroids displayed impaired basement membrane assembly. Furthermore, conditioned medium (CM) from embryonic endothelial progenitor cells (eEPCs) rescued the folliculogenesis defects of both Smad1/5dKO and VegfaKO thyroids. Laminin α1, β1 and γ1, abundantly released by eEPCs into CM, were crucial for folliculogenesis. Thus, epithelial Smad signaling and endothelial cell invasion promote folliculogenesis via assembly of the basement membrane.
Index terms / Keywords Thyroid; Smad1; Smad5; follicle; Epithelium; Extracellular matrix; Mouse
DOI doi: 10.1242/dev.134171