Title: Thyroid follicle development requires Smad1/Smad5- and endothelial-dependent basement membrane assembly
Authors: Villacorte, Mylah ×
Delmarcelle, Anne-Sophie
Lernoux, Manon
Bouquet, Mahé
Lemoine, Pascale
Bolsée, Jennifer
Umans, Lieve
de Sousa Lopes, Susana Chuva
Van Der Smissen, Patrick
Sasaki, Takako
Bommer, Guido
Henriet, Patrick
Refetoff, Samuel
Lemaigre, Frédéric P
Zwijsen, An
Courtoy, Pierre J
Pierreux, Christophe E #
Issue Date: Jun-2016
Publisher: Company of Biologists
Series Title: Development vol:143 issue:11
Article number: dev.134171
Abstract: Thyroid follicles, the functional units of the thyroid gland, are delineated by a monolayer of thyrocytes resting on a continuous basement membrane. Developmental mechanisms whereby follicles are formed by reorganization of a non-structured mass of non-polarized epithelial cells (folliculogenesis) largely unknown. Here we 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 (Smad1/5(dKO)) displayed growth retardation, hypothyroidism and defective follicular architecture. In Smad1/5(dKO)embryonic thyroids, epithelial cells remained associated in large clusters and formed small follicles. Although similar follicular defects are found in Vegfa(KO)thyroids, Smad1/5(dKO)thyroids had normal endothelial cell density yet impaired endothelial differentiation. Interestingly, both Vegfa(KO)and Smad1/5(dKO)thyroids displayed impaired basement membrane assembly. Furthemore, conditioned medium (CM) from embryonic endothelial progenitor cells (eEPC) rescued the folliculogenic defects of both Smad1/5(dKO)and Vegfa(KO)thyroids. Laminin α1β1γ1, abundantly released by eEPC into CM, was critically required for folliculogenesis. Thus, epithelial Smad signaling and endothelial cell invasion promote folliculogenesis via assembly of the basement membrane.
ISSN: 0950-1991
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
dev.134171.full.pdfOA article Accepted 1998KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members


All items in Lirias are protected by copyright, with all rights reserved.