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Intraflagellar Transport Complex B Proteins Regulate The Hippo Effector Yap1 During Cardiogenesis

Marina Peralta, Katerina Jerabkova, Tommaso Lucchesi, Laia Ortiz Lopez, Benjamin Vitre, Dong Han, Laurent Guillemot, Chaitanya Dingare, Izabela Sumara, Nadia Mercader, Virginie Lecaudey, Benedicte Delaval, Sigolène M. Meilhac, Julien Vermot

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AbstractCilia and the intraflagellar transport (IFT) proteins involved in ciliogenesis are associated with congenital heart diseases (CHD). However, the molecular links between cilia, IFT proteins and cardiogenesis are yet to be established. Using a combination of biochemistry, genetics, and live imaging methods, we show that IFT complex B proteins (Ift88, Ift54 and Ift20) modulate the Hippo pathway effector YAP1 in zebrafish and mouse. We demonstrate that this interaction is key to restrict the formation of the proepicardium and the myocardium. In cellulo experiments suggest that IFT88 and IFT20 interact with YAP1 in the cytoplasm and functionally modulates its activity, identifying a molecular link between cilia related proteins and the Hippo pathway. Taken together, our results highlight a novel role for IFT complex B proteins during cardiogenesis and shed light on an unexpected mechanism of action for ciliary proteins in YAP1 regulation. These findings provide mechanistic insights into a non-canonical role for cilia related proteins during cardiogenesis.