LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis

Huai-Bin Hu, Zeng-Qing Song, Guang-Ping Song, Sen Li, Hai-Qing Tu, Min Wu, Yu-Cheng Zhang, Jin-Feng Yuan, Ting-Ting Li, Pei-Yao Li, Yu-Ling Xu, Xiao-Lin Shen, Qiu-Ying Han, Ai-Ling Li, Tao Zhou, Jerold Chun, Xue-Min Zhang () and Hui-Yan Li ()
Additional contact information
Huai-Bin Hu: National Center of Biomedical Analysis
Zeng-Qing Song: National Center of Biomedical Analysis
Guang-Ping Song: National Center of Biomedical Analysis
Sen Li: National Center of Biomedical Analysis
Hai-Qing Tu: National Center of Biomedical Analysis
Min Wu: National Center of Biomedical Analysis
Yu-Cheng Zhang: National Center of Biomedical Analysis
Jin-Feng Yuan: National Center of Biomedical Analysis
Ting-Ting Li: National Center of Biomedical Analysis
Pei-Yao Li: National Center of Biomedical Analysis
Yu-Ling Xu: National Center of Biomedical Analysis
Xiao-Lin Shen: National Center of Biomedical Analysis
Qiu-Ying Han: National Center of Biomedical Analysis
Ai-Ling Li: National Center of Biomedical Analysis
Tao Zhou: National Center of Biomedical Analysis
Jerold Chun: Sanford Burnham Prebys Medical Discovery Institute
Xue-Min Zhang: National Center of Biomedical Analysis
Hui-Yan Li: National Center of Biomedical Analysis

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular—LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.

Date: 2021
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DOI: 10.1038/s41467-021-20986-y

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