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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 Shh signaling. Interestingly, it is the non-canonical Shh signaling that represses Aqp1 and Atp1a2 expression by Smo\/G\u03b1i\/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 developing choroid plexus, a derepression of Aqp1 and Atp1a2, and ultimately, an increased CSF production. Hence, developmental dynamics of choroid plexus multicilia dampens the Shh signaling intensity to promote CSF production.<\/jats:p>","DOI":"10.1101\/2025.01.21.633415","type":"posted-content","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T09:10:15Z","timestamp":1737537015000},"source":"Crossref","is-referenced-by-count":0,"title":["Multicilia dynamically transduce Shh signaling to regulate choroid plexus functions"],"prefix":"10.64898","author":[{"given":"Suifang","family":"Mao","sequence":"first","affiliation":[{"name":"Division of Cellular and Developmental Biology, MCB department, University of California at Berkeley, Berkeley, CA 94705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Cellular and Developmental Biology, MCB department, University of California at Berkeley, Berkeley, CA 94705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shibo","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Cellular and Developmental Biology, MCB department, University of California at Berkeley, Berkeley, CA 94705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Pang","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA"},{"name":"Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Jovanovic","sequence":"additional","affiliation":[{"name":"Division of Cellular and Developmental Biology, MCB department, University of California at Berkeley, Berkeley, CA 94705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Division of Cellular and Developmental Biology, MCB department, University of California at Berkeley, Berkeley, CA 94705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cellular and Developmental Biology, MCB department, University of California at Berkeley, Berkeley, CA 94705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinying","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Cellular and Developmental Biology, MCB department, University of California at Berkeley, Berkeley, CA 94705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael F.","family":"Wendland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cellular and Developmental Biology, MCB department, University of California at Berkeley, Berkeley, CA 94705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Chi","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cellular and Developmental Biology, MCB department, University of California at Berkeley, Berkeley, CA 94705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Semil P.","family":"Choksi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA; 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