Inhibitory input directs astrocyte morphogenesis through glial GABA B R
Inhibitory input directs astrocyte morphogenesis through glial GABA B R
Abstract Communication between neurons and glia plays an important role in establishing and maintaining higher order brain function. Astrocytes are endowed with complex morphologies which places their peripheral processes in close proximity to neuronal synapses and directly contributes to their regulation of brain circuits. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unknown. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABABR and that its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function. Expression of GABABR in developing astrocytes is regulated in a region-specific manner by SOX9 or NFIA and deletion of these transcription factors results in region-specific defects in astrocyte morphogenesis, which is conferred by interactions with transcription factors exhibiting region-restricted patterns of expression. Together our studies identify input from inhibitory neurons and astrocytic GABABR as universal regulators of morphogenesis, while further revealing a combinatorial code of region-specific transcriptional dependencies for astrocyte development that is intertwined with activity-dependent processes.
Deneen Benjamin、Chen Hsiao-Chi、Harmanci Akdes Serin、Lee Zhung-Fu、Cheng Yi-Ting、Woo Junsung、Luna-Figueroa Estefania
Center for Cancer Neuroscience, Baylor College of Medicine||Program in Developmental Biology, Baylor College of Medicine||Center for Cell and Gene Therapy, Baylor College of Medicine||Development, Disease, Models, and Therapeutics Graduate Program, Baylor College of Medicine||Cancer Cell Biology Graduate Program, Baylor College of Medicine||Department of Neurosurgery, Baylor College of MedicineCenter for Cancer Neuroscience, Baylor College of Medicine||Cancer Cell Biology Graduate Program, Baylor College of MedicineCenter for Cancer Neuroscience, Baylor College of Medicine||Center for Cell and Gene Therapy, Baylor College of MedicineCenter for Cancer Neuroscience, Baylor College of Medicine||Development, Disease, Models, and Therapeutics Graduate Program, Baylor College of MedicineCenter for Cancer Neuroscience, Baylor College of Medicine||Program in Developmental Biology, Baylor College of MedicineCenter for Cancer Neuroscience, Baylor College of Medicine||Center for Cell and Gene Therapy, Baylor College of MedicineCenter for Cancer Neuroscience, Baylor College of Medicine||Center for Cell and Gene Therapy, Baylor College of Medicine
细胞生物学分子生物学生理学
Deneen Benjamin,Chen Hsiao-Chi,Harmanci Akdes Serin,Lee Zhung-Fu,Cheng Yi-Ting,Woo Junsung,Luna-Figueroa Estefania.Inhibitory input directs astrocyte morphogenesis through glial GABA B R[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/2023.03.14.532493.点此复制
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