Biology subjects

Bensimon-Brito, A.

Publications and source records attributed to Bensimon-Brito, A..

2 recordsLinked to original sources

bioRxiv2020

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

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 have often been associated with impaired TGF-{beta} signaling. To further investigate the role of TGF-{beta} signaling in OFT formation, we generated zebrafish lacking the type I TGF-{beta} receptor Alk5 and found a strikingly specific dilation of the OFT. alk5 mutants also exhibit increased EC numbers, extracellular matrix (ECM) and SMC disorganization. Surprisingly, endothelial-specific alk5 overexpression in alk5 mutants rescues both endothelial and SMC defects. Furthermore, modulation of the ECM gene fibulin-5, a TGF-{beta} target, partially restores 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.

developmental biology↗

bioRxiv2019

Cardiac valve regeneration in adult zebrafish: importance of TGF-β signaling in new tissue formation

Cardiac valve disease can lead to severe cardiac dysfunction and is thus a frequent cause of morbidity and mortality. Its main treatment is valve replacement, which is currently greatly limited by the poor recellularization and tissue formation potential of the implanted valves. As we still lack suitable animal models to identify modulators of these processes, here we used the adult zebrafish and found that, upon valve decellularization, they initiate a striking regenerative program that leads to the formation of new functional valves. After injury, endothelial and kidney marrow-derived cells undergo cell cycle re-entry and differentiate into new extracellular matrix-secreting valve cells. The Transforming Growth Factor beta (TGF{beta}) signaling pathway promotes this process by enhancing progenitor cell proliferation as well as valve cell differentiation. These findings reveal a key role for TGF{beta} signaling in valve regeneration and also establish the zebrafish as a model to identify and test factors promoting valve recellularization and growth.

developmental biology↗