Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1
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ABSTRACT:
PROVIDER: PRJNA503873 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8159050_1.fastq.gz | Fastqsanger.gz | |||
| SRR8159050_2.fastq.gz | Fastqsanger.gz | |||
| SRR8159051_1.fastq.gz | Fastqsanger.gz | |||
| SRR8159051_2.fastq.gz | Fastqsanger.gz | |||
| SRR8159052_1.fastq.gz | Fastqsanger.gz |
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Project description:Astrocytic morphogenesis and maturation are critical steps in CNS development. The time window of astrocyte morphological development is well defined, but the molecular underpinnings are still unclear. BDNF is a critical growth factor involved in the development of the CNS, including synapse refinement. Here we demonstrate the BDNF receptor at Ntrk2 is enriched in astrocytes relative to all CNS cell populations. RNA sequencing indicates Ntrk2 falls in the top 0.001% of all gene transcripts expressed in juvenile astrocytes, almost exclusively due to truncated TrkB.T1. Astrocyte complexity is increased in the presence of BNDF in vitro, which is dependent upon the presence of TrkB.T1. Furthermore, deletion of TrkB.T1 in vivo revealed astrocytes with significantly reduced volume and branching complexities. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis. Together, these data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphogenesis and indicate this signaling may contribute to astrocyte regulation of neuronal synapse development.
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Project description:Brain-derived neurotrophic factor (BDNF) is a critical growth factor involved in the maturation of the CNS, including neuronal morphology and synapse refinement. Herein, we demonstrate astrocytes express high levels of BDNF's receptor, TrkB (in the top 20 of protein-coding transcripts), with nearly exclusive expression of the truncated isoform, TrkB.T1, which peaks in expression during astrocyte morphological maturation. Using a novel culture paradigm, we show that astrocyte morphological complexity is increased in the presence of BDNF and is dependent upon BDNF/TrkB.T1 signaling. Deletion of TrkB.T1, globally and astrocyte-specifically, in mice revealed morphologically immature astrocytes with significantly reduced volume, as well as dysregulated expression of perisynaptic genes associated with mature astrocyte function. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis or function. These data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphological maturation, a critical process for CNS development.
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Project description:Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocytic infiltration of the neuropil alters synaptic connectivity. Here we show that astrocyte morphogenesis in the mouse cortex depends on direct contact with neuronal processes and occurs in parallel with the growth and activity of synaptic circuits. The neuroligin family cell adhesion proteins NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, the formation and function of cortical excitatory synapses are diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a previously undescribed mechanism of action for neuroligins and link astrocyte morphogenesis to synaptogenesis. Because neuroligin mutations have been implicated in various neurological disorders, these findings also point towards an astrocyte-based mechanism of neural pathology.
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