Primary cilia shape postnatal astrocyte development through Sonic Hedgehog signaling

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.