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

Gang Zhai; Jia Song; Tingting Shu; Junjun Yan; Xia Jin; Jiangyan He; Zhan Yin

doi:10.1016/j.jgg.2017.03.006

Volume 44 Issue 6

Jun. 2017

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

doi: 10.1016/j.jgg.2017.03.006

Gang Zhai^a,
Jia Song^{a, b},
Tingting Shu^{a, b},
Junjun Yan^{a, b},
Xia Jin^a,
Jiangyan He^a,
Zhan Yin^a

a
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
b
University of the Chinese Academy of Sciences, Beijing 100049, China

More Information

Corresponding author: E-mail address: zyin@ihb.ac.cn (Zhan Yin)
Received Date: 2016-08-11
Accepted Date: 2017-03-30
Rev Recd Date: 2017-03-28

Available Online: 2017-04-27

Publish Date: 2017-06-20

Abstract

Abstract

Liver receptor homolog-1 (LRH-1) is an orphan nuclear receptor that is critical for the growth and proliferation of cancer cells and other biological processes, including lipid transportation and metabolism, sexual determination and steroidogenesis. However, because homozygouslrh-1^−/− mice die in utero, the regulatory mechanisms involved in embryonic development mediated by this receptor are poorly understood. In the present study, we performed transcription activator-like effector nuclease (TALEN)-mediated loss-of-function assays, taking advantage of zebrafish external fertilization, to investigate 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 G1 to S phase), but not cell apoptosis. Biochemical analysis revealed that LRH-1 augments the transcriptional activity of β-catenin 1 and 2 via physical interactions. Screening the specific ligand(s) sensed by LRH-1 during organogenesis revealed that phosphatidylcholine (PC), a potential ligand, is the upstream target of LRH-1 during endoderm development. These data provide evidence for the crosstalk between the PC/LRH-1 and Wnt/β-catenin signaling pathways during the expansion growth of endoderm organs.
- Zebrafish,
- LRH-1,
- Phosphatidylcholine,
- Wnt/β-catenin signaling,
- Development

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