S1P-Yap1 Signaling Regulates Endoderm Formation Required for Cardiac Precursor Cell Migration in Zebrafish

Abstract

To form the primary heart tube in zebrafish, bilateral cardiac precursor cells (CPCs) migrate toward the midline beneath the endoderm. Mutants lacking endoderm and fish with defective sphingosine 1-phosphate (S1P) signaling exhibit cardia bifida. Endoderm defects lead to the lack of foothold for the CPCs, whereas the cause of cardia bifida in S1P signaling mutants remains unclear. Here we show that S1P signaling regulates CPC migration through Yes-associated protein 1 (Yap1)-dependent endoderm survival. Cardia bifida seen in spns2 (S1P transporter) morphants and s1pr2 (S1P receptor-2) morphants could be rescued by endodermal expression of nuclear localized form of yap1. yap1 morphants had decreased expression of the Yap1/Tead target connective tissue growth factor a (Ctgfa) and consequently increased endodermal cell apoptosis. Consistently, ctgfa morphants showed defects of the endodermal sheet and cardia bifida. Collectively, we show that S1pr2/Yap1-regulated ctgfa expression is essential for the proper endoderm formation required for CPC migration.

Yap/Taz transcriptional activity in endothelial cells promotes intramembranous ossification via the BMP pathway

“…1a and Supplemental Fig. S1)23. 293T cells were transfected with pFR-Luc and pcDNA3.1-Gal4-hTead2ΔN for measuring the transcriptional activities of zYap or zTaz cells.…”

Yap control of tissue growth relies on cell density and F-actin in zebrafish fin regeneration

“…DN-yap transgenic fish were validated by addressing the previously demonstrated requirement of Yap for cardiac precursor cell migration, using morpholinos (supplementary material Fig. S2B-M) (Fukui et al, 2014;Miesfeld and Link, 2014). Moreover, when we performed immunostainings against RFP and Yap in both transgenic lines, we observed colocalization (supplementary material Fig.…”

YAP and TAZ: a nexus for Hippo signaling and beyond

“…GPCR-driven pathologies can be mediated via dysregulated YAP/TAZ [7,11–13,116] and examples of FDA-approved drugs targeting GPCRs modifying YAP/TAZ activity are known [10,117]. Several notable GPCR ligands play crucial roles in intestinal regeneration [118], development [119], and stem cell pluripotency [120,121] – biological processes where YAP and TAZ are known to be key mediators [6,74,107]. Importantly, S1P–YAP signaling was shown to be important for cardiac precursors in zebrafish [119], but whether these effects by LPA, S1P, and other GPCR ligands in general are mediated via activation of YAP/TAZ transcriptional activity in vivo in nonpathological conditions is currently not well understood.…”

“…Several notable GPCR ligands play crucial roles in intestinal regeneration [118], development [119], and stem cell pluripotency [120,121] – biological processes where YAP and TAZ are known to be key mediators [6,74,107]. Importantly, S1P–YAP signaling was shown to be important for cardiac precursors in zebrafish [119], but whether these effects by LPA, S1P, and other GPCR ligands in general are mediated via activation of YAP/TAZ transcriptional activity in vivo in nonpathological conditions is currently not well understood. It is worthwhile to expand these correlative relationships with loss-of-function experiments in mammalian animal models.…”