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  Endothelial TGF-beta signaling instructs smooth muscle cell development in the cardiac outflow tract

Boezio, G. L. M., Bensimon-Brito, A., Piesker, J., Guenther, S., Helker, C. S. M., & Stainier, D. Y. R. (2020). Endothelial TGF-beta signaling instructs smooth muscle cell development in the cardiac outflow tract. ELIFE, 9: e57603. doi:10.7554/eLife.57603.

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Boezio, Giulia L. M.1, Autor           
Bensimon-Brito, Anabela1, Autor           
Piesker, Janett2, Autor           
Guenther, Stefan3, Autor           
Helker, Christian S. M.1, Autor           
Stainier, Didier Y. R.1, Autor           
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              
2Electron Microscopy, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591707              
3Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

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 Zusammenfassung: The development of the cardiac outflow tract (OFT), which connects the heart to the great arteries, relies on a complex crosstalk between endothelial (ECs) and smooth muscle (SMCs) cells. Defects in OFT development can lead to severe malformations, including aortic aneurysms, which are frequently associated with impaired TGF-beta signaling. To better understand the role of TGF-beta signaling in OFT formation, we generated zebrafish lacking the TGF-beta receptor Alk5 and found a strikingly specific dilation of the OFT: alk5-/- OFTs exhibit increased EC numbers as well as extracellular matrix (ECM) and SMC disorganization. Surprisingly, endothelial-specific alk5 overexpression in alk5-/- rescues the EC, ECM, and SMC defects. Transcriptomic analyses reveal downregulation of the ECM gene fibulin-5, which when overexpressed in ECs ameliorates OFT morphology and function. These findings reveal a new requirement for endothelial TGF-beta signaling in OFT morphogenesis and suggest an important role for the endothelium in the etiology of aortic malformations.

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 Datum: 2020-09-29
 Publikationsstatus: Online veröffentlicht
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 Identifikatoren: ISI: 000576679100001
DOI: 10.7554/eLife.57603
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Titel: ELIFE
Genre der Quelle: Zeitschrift
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Seiten: - Band / Heft: 9 Artikelnummer: e57603 Start- / Endseite: - Identifikator: ISSN: 2050-084X