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Sphingosine-1-Phosphate Receptor 1 regulates competition dependent astrocyte morphogenesis and tiling in murine
Jean Patrick M Gonzales1, Connor Tuck1, Surya Chandra Rao Thummu1
1Department of Cellular, Molecular and Genetic Medicine, School of Medicine and the Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, Virginia, 23298, USA.
Biorxiv : the Preprint Server for Biology
|April 10, 2026
Summary
Sphingosine-1-phosphate receptor 1 (S1PR1) controls astrocyte shape and tiling in the developing brain. This lipid signaling pathway is crucial for astrocyte development and brain homeostasis.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Astrocytes are crucial glial cells that maintain brain homeostasis.
- Astrocyte morphology and tiling are essential for neural circuit function but poorly understood.
- Neuronal contact influences astrocyte morphology, but the underlying mechanisms are unclear.
Purpose of the Study:
- To investigate the role of sphingosine-1-phosphate receptor 1 (S1PR1) in astrocyte morphogenesis and tiling in vivo.
- To elucidate the mechanisms by which neuronal activity regulates S1PR1 expression in astrocytes.
Main Methods:
- Utilized a human astrocyte-mouse neuron co-culture system.
- Generated astrocyte-specific S1PR1 knockout mouse models.
- Employed adeno-associated viral labeling techniques for in vivo studies.
Main Results:
- S1PR1 regulates astrocyte morphogenesis in a cortical layer-specific manner in vivo.
- S1PR1 is essential for competition-driven astrocyte tiling and morphogenesis during brain development.
- JAK-STAT3 signaling mediates neuronal contact-induced S1PR1 expression in astrocytes.
Conclusions:
- S1PR1 is a key regulator of astrocyte morphogenesis and tiling in the developing murine cortex.
- Lipid signaling via S1PR1 plays a critical role in establishing astrocyte organization.
- Understanding S1PR1 function provides insights into brain development and homeostasis.
