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Related Experiment Video

Updated: May 29, 2025

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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Multicilia dynamically transduce Shh signaling to regulate choroid plexus functions.

Suifang Mao, Rui Song, Shibo Jin

    Biorxiv : the Preprint Server for Biology
    |February 3, 2025
    PubMed
    Summary

    Defective choroid plexus cilia cause neonatal hydrocephalus by altering water and ion transporter expression. Developmental changes in these unique sensory cilia regulate cerebrospinal fluid production via Shh signaling.

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    Area of Science:

    • Neuroscience
    • Cell Biology
    • Developmental Biology

    Background:

    • The choroid plexus epithelium, featuring multiciliated cells, is crucial for cerebrospinal fluid (CSF) production.
    • Dysfunctional cilia in the choroid plexus are linked to neurological conditions like hydrocephalus.

    Purpose of the Study:

    • To investigate the role of choroid plexus multicilia in regulating CSF production and their connection to hydrocephalus.
    • To elucidate the signaling pathways and molecular mechanisms underlying choroid plexus ciliogenesis and function.

    Main Methods:

    • Analysis of choroid plexus ciliogenesis and intraflagellar transport in relation to hydrocephalus.
    • Investigation of aquaporin 1 (Aqp1) and sodium-potassium ATPase alpha 2 subunit (Atp1a2) expression.
    • Examination of Sonic hedgehog (Shh) signaling pathways, including canonical and non-canonical routes.
    • Ultrastructural analysis of choroid plexus cilia and their developmental changes.

    Main Results:

    • Defective ciliogenesis or intraflagellar transport in the choroid plexus leads to neonatal hydrocephalus, associated with increased Aqp1 and Atp1a2 expression.
    • Choroid plexus multicilia function as sensory cilia, transducing both canonical and non-canonical Shh signaling.
    • Non-canonical Shh signaling, mediated by Smo/Gαi/cAMP, represses Aqp1 and Atp1a2 expression.
    • Unique ciliary ultrastructure and decreasing ciliary length during development lead to reduced Shh signaling, derepression of Aqp1/Atp1a2, and increased CSF production.

    Conclusions:

    • Developmental dynamics of choroid plexus multicilia play a key role in dampening Shh signaling intensity.
    • This modulation of Shh signaling ultimately promotes cerebrospinal fluid production and prevents hydrocephalus.