LRH-1 senses signaling from phosphatidylcholine to regulate theexpansion growth of digestive organs via synergy with Wnt/β-cateninsignaling in zebrafish

Liver receptor homolog-1 （LRH-1） is an orphan nuclear receptor that is critical for the growth andproliferation of cancer cells and other biological processes, including lipid transportation and meta-bolism, sexual determination and steroidogenesis. However, because homozygous lrh-1-/- mice die inutero, the regulatory mechanisms involved in embryonic development mediated by this receptor arepoorly understood. In the present study, we performed transcription activator-like effector nuclease（TALEN）-mediated loss-of-function assays, taking advantage of zebrafish external fertilization, toinvestigate the function of lrh- 1. The digestive organs were affected by lrh-1 depletion as a result of cell-cycle arrest （at the checkpoint of Gl to S phase）, but not cell apoptosis. Biochemical analysis revealed thatLRH-1 augments the transcriptional activity of β-catenin 1 and 2 via physical interactions. Screening thespecific ligand（s） sensed by LRH-1 during organogenesis revealed that phosphatidylcholine （PC）, a po-tential ligand, is the upstream target of LRH-1 during endoderm development. These data provide evi-dence for the crosstalk between the PC]LRH-1 and Wnt/β-catenin signaling pathways during theexpansion growth of endoderm organs.