miR-34/449 miRNAs regulate choroid plexus ciliogenesis to control cerebrospinal fluid production

Abstract

A developmental increase in cerebrospinal fluid (CSF) production during development is essential for neuronal growth and ventricular expansion. A key regulator of CSF production is the specialized sensory multicilia of the choroid plexus (ChP), which mediate non-canonical Sonic hedgehog (Shh) signaling to suppress water channel and ion transporter expression, thereby limiting CSF production. ChP multicilia progressively shortens during development, attenuating Shh signaling and promoting CSF production. Here, we identify miR-34/449 miRNAs as essential regulators of ChP multiciliogenesis. Whereas mutations in canonical ciliogenesis genes elevate CSF production and contribute to hydrocephaly, deletion of miR-34/449 reduces CSF volume and causes microcephaly. Loss of miR-34/449 miRNAs causes excessive basal body amplification, defective basal body docking, and failure of developmental multiciliary shortening. Consequently, miR-34/449-deficient ChP cilia remain abnormally long and fail to attenuate Shh signaling, resulting in sustained repression of water channel and ion transporter expression and reduced CSF production. Mechanistically, miR-34/449 miRNAs directly target Gmnc, a master transcriptional regulator of multiciliogenesis, to restrain basal body amplification and promote basal body docking. Together, our findings identify miR-34/449 miRNAs as critical regulators of ChP multiciliogenesis and establish the developmental remodeling of ChP multicilia as a mechanism to couple Shh signaling dynamics to developmental control of CSF production.

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BibTeX RIS

BibTeX

@misc{mao2026mir34449,
  title = {{miR-34/449 miRNAs regulate choroid plexus ciliogenesis to control cerebrospinal fluid production}},
  author = {S. Mao and R. Song and A. Jovanovic and S. Jin and S. Pang and D. M. Jorgens and M. F. Wendland and A. Zimmerman and D. Lin and Z. Xuan and C. S. Xu and H. F. Hess and S. Upadhyayula and L. He},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.30.747939},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.30.747939v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - miR-34/449 miRNAs regulate choroid plexus ciliogenesis to control cerebrospinal fluid production
AU  - S. Mao
AU  - R. Song
AU  - A. Jovanovic
AU  - S. Jin
AU  - S. Pang
AU  - D. M. Jorgens
AU  - M. F. Wendland
AU  - A. Zimmerman
AU  - D. Lin
AU  - Z. Xuan
AU  - C. S. Xu
AU  - H. F. Hess
AU  - S. Upadhyayula
AU  - L. He
PY  - 2026
DA  - 2026/08/30
PB  - bioRxiv
DO  - 10.64898/2026.08.30.747939
UR  - https://www.biorxiv.org/content/10.64898/2026.08.30.747939v1
AB  - A developmental increase in cerebrospinal fluid (CSF) production during development is essential for neuronal growth and ventricular expansion. A key regulator of CSF production is the specialized sensory multicilia of the choroid plexus (ChP), which mediate non-canonical Sonic hedgehog (Shh) signaling to suppress water channel and ion transporter expression, thereby limiting CSF production. ChP multicilia progressively shortens during development, attenuating Shh signaling and promoting CSF production. Here, we identify miR-34/449 miRNAs as essential regulators of ChP multiciliogenesis. Whereas mutations in canonical ciliogenesis genes elevate CSF production and contribute to hydrocephaly, deletion of miR-34/449 reduces CSF volume and causes microcephaly. Loss of miR-34/449 miRNAs causes excessive basal body amplification, defective basal body docking, and failure of developmental multiciliary shortening. Consequently, miR-34/449-deficient ChP cilia remain abnormally long and fail to attenuate Shh signaling, resulting in sustained repression of water channel and ion transporter expression and reduced CSF production. Mechanistically, miR-34/449 miRNAs directly target Gmnc, a master transcriptional regulator of multiciliogenesis, to restrain basal body amplification and promote basal body docking. Together, our findings identify miR-34/449 miRNAs as critical regulators of ChP multiciliogenesis and establish the developmental remodeling of ChP multicilia as a mechanism to couple Shh signaling dynamics to developmental control of CSF production.
ER  -

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