Intraflagellar Transport Complex B Proteins Regulate the Hippo Effector Yap1 during Cardiogenesis

Cilia and the intraflagellar transport (IFT) proteins involved in ciliogenesis are associated with congenital heart diseases (CHDs). 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 modulate its activity, identifying a molecular link between cilia-related proteins and the Hippo pathway. Taken together, our results highlight a noncanonical role for IFT complex B proteins during cardiogenesis and shed light on a mechanism of action for ciliary proteins in YAP1 regulation. [Display omitted] •IFT proteins restrict proepicardial and myocardial development•IFT proteins act independently of primary cilia in this process•IFT proteins modulate BMP signaling by tuning Yap1-Tead activity•IFT88 and IFT20 interact with YAP1 in the cytoplasm to set Yap1-Tead activity Peralta et al. show that intraflagellar transport (IFT) complex B proteins (Ift88, Ift54, and Ift20) modulate the Hippo pathway effector Yap1 in zebrafish and mouse. This cytoplasmic interaction is key to restrict proepicardial and myocardial development.