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Using Primary Neurosphere Cultures to Study Primary Cilia
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Primary cilia shape postnatal astrocyte development through Sonic Hedgehog signaling.

Rachel Bear1,2, Steven A Sloan1, Tamara Caspary1

  • 1Department of Human Genetics, Emory University School of Medicine, 615 Michael Street Suite 301, Atlanta, GA 30322, USA.

Journal of Cell Science
|March 20, 2025
PubMed
Summary

Astrocyte cilia are essential for Sonic Hedgehog (Shh) signaling during brain development. Their loss impairs astrocyte proliferation and maturation, offering insights into neurodevelopmental disorders.

Keywords:
AstrocytesCiliaDevelopmentMorphologyProliferationSonic Hedgehog

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Primary cilia are critical signaling hubs regulating cellular processes, including neuron and glia development.
  • Astrocyte cilia function in development is understudied, yet astrocyte and cilia dysfunction are linked to neurodevelopmental disorders.

Purpose of the Study:

  • To investigate the role of cilia in astrocyte development and Sonic Hedgehog (Shh) signaling.
  • To determine the impact of astrocyte cilia loss on astrocyte proliferation and maturation.

Main Methods:

  • In vivo genetic ablation of astrocyte cilia at distinct developmental stages.
  • Analysis of Sonic Hedgehog (Shh) transcriptional targets.
  • Assessment of astrocyte proliferation and morphology.

Main Results:

  • A subpopulation of developing astrocytes in the prefrontal cortex express the ciliary protein ARL13B and are ciliated.
  • Loss of astrocyte cilia decreased Shh signaling activity in both immature and mature astrocytes.
  • Astrocyte cilia ablation led to reduced proliferation in immature astrocytes and enlarged morphology in mature astrocytes.

Conclusions:

  • Astrocyte cilia are required for Shh signaling throughout astrocyte development.
  • Astrocyte cilia play crucial roles in regulating astrocyte proliferation and maturation.
  • Findings advance understanding of astrocyte development, cilia function, and neurodevelopmental disorders.