Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions
Summary: The choroid plexus is a major site for cerebrospinal fluid (CSF) production, characterized by a multiciliated epithelial monolayer that regulates CSF production. We demonstrate that defective choroid plexus ciliogenesis or intraflagellar transport yields neonatal hydrocephalus, at least in...
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Elsevier
2025-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725001548 |
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| author | Suifang Mao Rui Song Shibo Jin Song Pang Aleksandra Jovanovic Adam Zimmerman Peng Li Xinying Wu Michael F. Wendland Kerry Lin Wei-Chi Chen Semil P. Choksi Gang Chen Michael J. Holtzman Jeremy F. Reiter Ying Wan Zhenyu Xuan Yang K. Xiang C. Shan Xu Srigokul Upadhyayula Harald F. Hess Lin He |
| author_facet | Suifang Mao Rui Song Shibo Jin Song Pang Aleksandra Jovanovic Adam Zimmerman Peng Li Xinying Wu Michael F. Wendland Kerry Lin Wei-Chi Chen Semil P. Choksi Gang Chen Michael J. Holtzman Jeremy F. Reiter Ying Wan Zhenyu Xuan Yang K. Xiang C. Shan Xu Srigokul Upadhyayula Harald F. Hess Lin He |
| author_sort | Suifang Mao |
| collection | DOAJ |
| description | Summary: The choroid plexus is a major site for cerebrospinal fluid (CSF) production, characterized by a multiciliated epithelial monolayer that regulates CSF production. We demonstrate that defective choroid plexus ciliogenesis or intraflagellar transport yields neonatal hydrocephalus, at least in part due to increased water channel Aqp1 and ion transporter Atp1a2 expression. We demonstrate choroid plexus multicilia as sensory cilia, transducing both canonical and non-canonical Sonic Hedgehog (Shh) signaling. Interestingly, it is the non-canonical Shh signaling that represses Aqp1 and Atp1a2 expression by the Smoothened (Smo)/Gαi/cyclic AMP (cAMP) pathway. Choroid plexus multicilia exhibit unique ciliary ultrastructure, carrying features of both primary and motile cilia. Unlike most cilia that elongate during maturation, choroid plexus ciliary length decreases during development, causing a decline of Shh signaling intensity in the developing choroid plexus, a derepression of Aqp1 and Atp1a2, and, ultimately, increased CSF production. Hence, the developmental dynamics of choroid plexus multicilia dampens the Shh signaling intensity to promote CSF production. |
| format | Article |
| id | doaj-art-afd461f17d574ec5bbf3dcb0a3a93cc2 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-afd461f17d574ec5bbf3dcb0a3a93cc22025-08-20T01:57:40ZengElsevierCell Reports2211-12472025-03-0144311538310.1016/j.celrep.2025.115383Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functionsSuifang Mao0Rui Song1Shibo Jin2Song Pang3Aleksandra Jovanovic4Adam Zimmerman5Peng Li6Xinying Wu7Michael F. Wendland8Kerry Lin9Wei-Chi Chen10Semil P. Choksi11Gang Chen12Michael J. Holtzman13Jeremy F. Reiter14Ying Wan15Zhenyu Xuan16Yang K. Xiang17C. Shan Xu18Srigokul Upadhyayula19Harald F. Hess20Lin He21Division of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USAJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USADepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USAChongqing Key Laboratory of Cytomics, Chongqing 400038, ChinaPulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USADepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USAChongqing Key Laboratory of Cytomics, Chongqing 400038, ChinaDepartment of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX 75080, USADepartment of Pharmacology, University of California at Davis, Davis, CA 95616, USA; VA Northern California Health Care System, Mather, CA 95655, USAJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Department of Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USADivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Corresponding authorJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Corresponding authorDivision of Cellular and Developmental Biology, MCB Department, University of California, Berkeley, Berkeley, CA 94705, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Corresponding authorSummary: The choroid plexus is a major site for cerebrospinal fluid (CSF) production, characterized by a multiciliated epithelial monolayer that regulates CSF production. We demonstrate that defective choroid plexus ciliogenesis or intraflagellar transport yields neonatal hydrocephalus, at least in part due to increased water channel Aqp1 and ion transporter Atp1a2 expression. We demonstrate choroid plexus multicilia as sensory cilia, transducing both canonical and non-canonical Sonic Hedgehog (Shh) signaling. Interestingly, it is the non-canonical Shh signaling that represses Aqp1 and Atp1a2 expression by the Smoothened (Smo)/Gαi/cyclic AMP (cAMP) pathway. Choroid plexus multicilia exhibit unique ciliary ultrastructure, carrying features of both primary and motile cilia. Unlike most cilia that elongate during maturation, choroid plexus ciliary length decreases during development, causing a decline of Shh signaling intensity in the developing choroid plexus, a derepression of Aqp1 and Atp1a2, and, ultimately, increased CSF production. Hence, the developmental dynamics of choroid plexus multicilia dampens the Shh signaling intensity to promote CSF production.http://www.sciencedirect.com/science/article/pii/S2211124725001548CP: Cell biology |
| spellingShingle | Suifang Mao Rui Song Shibo Jin Song Pang Aleksandra Jovanovic Adam Zimmerman Peng Li Xinying Wu Michael F. Wendland Kerry Lin Wei-Chi Chen Semil P. Choksi Gang Chen Michael J. Holtzman Jeremy F. Reiter Ying Wan Zhenyu Xuan Yang K. Xiang C. Shan Xu Srigokul Upadhyayula Harald F. Hess Lin He Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions Cell Reports CP: Cell biology |
| title | Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions |
| title_full | Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions |
| title_fullStr | Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions |
| title_full_unstemmed | Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions |
| title_short | Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions |
| title_sort | multicilia dynamically transduce sonic hedgehog signaling to regulate choroid plexus functions |
| topic | CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725001548 |
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