Reciprocal epithelial:endothelial paracrine interactions during thyroid development govern follicular organization and C-cells differentiation
| Autor: | Pierre Sonveaux, Celine Forez, Patrick Van Der Smissen, Sabrina Klotz, Mahé Bouquet, Christophe E. Pierreux, Pierre J. Courtoy, Anne-Christine Hick, Tamara Copetti, Jean-François Collet, Anne-Sophie Delmarcelle, Olivier Feron |
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| Rok vydání: | 2013 |
| Předmět: |
Calcitonin
Male Vascular Endothelial Growth Factor A endocrine system medicine.medical_specialty Endothelium Cellular differentiation Thyroid Gland Explants Biology VEGF-A Epithelium Mice Paracrine signalling Internal medicine medicine Animals Molecular Biology C-cells Thyroid Follicles Mice Knockout Polarity Stem Cells Endothelial Cells Gene Expression Regulation Developmental Cell Differentiation Epithelial Cells Cell Biology Paracrine control Vascular Endothelial Growth Factor Receptor-2 Cell biology Endothelial stem cell Vascular endothelial growth factor A medicine.anatomical_structure Endocrinology Female Folliculogenesis Stem cell Developmental Biology |
| Zdroj: | Developmental Biology. 381:227-240 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2013.04.022 |
| Popis: | The thyroid is a highly vascularized endocrine gland, displaying a characteristic epithelial organization in closed spheres, called follicles. Here we investigate how endothelial cells are recruited into the developing thyroid and if they control glandular organization as well as thyrocytes and C-cells differentiation. We show that endothelial cells closely surround, and then invade the expanding thyroid epithelial cell mass to become closely associated with nascent polarized follicles. This close and sustained endothelial:epithelial interaction depends on epithelial production of the angiogenic factor, Vascular Endothelial Growth Factor-A (VEGF-A), as its thyroid-specific genetic inactivation reduced the endothelial cell pool of the thyroid by >90%. Vegfa KO also displayed decreased C-cells differentiation and impaired organization of the epithelial cell mass into follicles. We developed an ex vivo model of thyroid explants that faithfully mimicks bilobation of the thyroid anlagen, endothelial and C-cells invasion, folliculogenesis and differentiation. Treatment of thyroid explants at e12.5 with a VEGFR2 inhibitor ablated the endothelial pool and reproduced ex vivo folliculogenesis defects observed in conditional Vegfa KO. In the absence of any blood supply, rescue by embryonic endothelial progenitor cells restored folliculogenesis, accelerated lumen expansion and stimulated calcitonin expression by C-cells. In conclusion, our data demonstrate that, in developing mouse thyroid, epithelial production of VEGF-A is necessary for endothelial cells recruitment and expansion. In turn, endothelial cells control epithelial reorganization in follicles and C-cells differentiation. |
| Databáze: | OpenAIRE |
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