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Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP Signaling.

Thanh Khoa Nguyen1, Sophia Baker1, Julienne Angtuaco1

  • 1Department of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USA.

Journal of Developmental Biology
|June 25, 2025
PubMed
Summary
This summary is machine-generated.

The Cannabinoid receptor 1 (Cnr1) is crucial for cilia development. Cnr1 regulates kidney multiciliated cells (MCCs) through cyclic AMP (cAMP) signaling and independently, impacting ciliopathies and kidney diseases.

Keywords:
Cnr1cAMP signalingcannabinoid receptorciliogenesisendocannabinoid pathwaykidneymulticiliated cell

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Area of Science:

  • Developmental Biology
  • Cell Biology
  • Physiology

Background:

  • Endocannabinoid signaling is vital for nervous system function, but its role in other tissues is under-explored.
  • Cannabinoid receptor 1 (Cnr1) is present in multiciliated cells (MCCs) and elevated in kidney disease, but its function in renal MCC development is unknown.

Purpose of the Study:

  • To investigate the role of Cnr1 in cilia development, specifically in renal MCCs during zebrafish embryogenesis.
  • To elucidate the signaling pathways, including cyclic AMP (cAMP), through which Cnr1 influences renal MCC development.

Main Methods:

  • Utilized genetic manipulation (loss of function) and pharmacological agents (agonism, antagonism, cAMP activator/inhibitor) in zebrafish embryos.
  • Assessed cilia development and renal MCC populations using observational and quantitative methods.
  • Examined the involvement of cAMP signaling in Cnr1-mediated MCC development.

Main Results:

  • Loss of function, agonism, and antagonism of Cnr1 all resulted in decreased mature renal MCC populations.
  • Cnr1 deficiency impaired cilia development across multiple tissues, including the pronephros and Kupffer's vesicle.
  • Forskolin (cAMP activator) rescued MCC defects in Cnr1 agonist-treated embryos, indicating a role for cAMP signaling.
  • SQ-22536 (cAMP inhibitor) and Cnr1 deficiency both reduced MCC populations, suggesting both cAMP-dependent and independent roles for Cnr1.

Conclusions:

  • Cnr1 is essential for cilia development and regulates renal MCCs via both cAMP-dependent and independent pathways.
  • These findings highlight Cnr1's critical role in renal MCC development and have implications for understanding ciliopathies and kidney diseases.