1. Thyroid follicle development requires Smad1/5- and endothelial cell-dependent basement membrane assembly
- Author
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Jennifer Bolsée, Anne-Sophie Delmarcelle, Lieve Umans, Susana M. Chuva de Sousa Lopes, Mylah Villacorte, Frédéric P. Lemaigre, Guido T. Bommer, Patrick Henriet, An Zwijsen, Samuel Refetoff, Christophe E. Pierreux, Pascale Lemoine, Patrick Van Der Smissen, Pierre J. Courtoy, Manon Lernoux, Takako Sasaki, and Mahé Bouquet
- Subjects
0301 basic medicine ,Follicle ,Vascular Endothelial Growth Factor A ,Mouse ,Organogenesis ,Thyroid Gland ,Thyroid follicle ,Epithelium ,Basement Membrane ,Laminin ,Thyroid ,Mice, Knockout ,biology ,Stem Cells ,Gene Expression Regulation, Developmental ,Extracellular matrix ,Basement membrane assembly ,Cell biology ,Endothelial stem cell ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,Bone Morphogenetic Proteins ,Folliculogenesis ,Signal Transduction ,Research Article ,Collagen Type IV ,Smad5 Protein ,medicine.medical_specialty ,endocrine system ,animal structures ,Smad1 Protein ,03 medical and health sciences ,Hypothyroidism ,Internal medicine ,medicine ,Animals ,Molecular Biology ,Thyroid Epithelial Cells ,Basement membrane ,Endothelial Cells ,Cell Biology ,030104 developmental biology ,Endocrinology ,Culture Media, Conditioned ,biology.protein ,Blood Vessels ,Smad1 ,Smad5 ,Developmental Biology - 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. ispartof: Development vol:143 issue:11 pages:1958-1970 ispartof: location:England status: published
- Published
- 2015