Delayed crosstalk between astrocytes and neurons leads to depressive-like behaviors
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ABSTRACT:
PROVIDER: PRJNA1190409 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31509312_1.fastq.gz | Fastqsanger.gz | |||
| SRR31509312_2.fastq.gz | Fastqsanger.gz | |||
| SRR31509313_1.fastq.gz | Fastqsanger.gz | |||
| SRR31509313_2.fastq.gz | Fastqsanger.gz | |||
| SRR31509314_1.fastq.gz | Fastqsanger.gz |
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Project description:The proper function establishment of nervous system is characterized by closely crosstalk among multiple cell types during the critical periods. Impeding or delaying the crosstalk results in abnormal neural functions and neurodevelopmental disorders. However, the lack of robust mouse models to study the crosstalk between astrocytes and neurons thus renders unclear the implications of impeding such interactions. Here we found that Egfr knockout led to the absence of astrocytes during the critical period of neuronal maturation, with recovery observed in adult mice, providing an exceptional opportunity to investigate the consequences of delaying crosstalk between astrocytes and neurons. We show that glial progenitor cells exhibit a rounded and smooth morphology, displaying few or no protrusions, in the absence of Egfr, which stands in stark contrast to the multi-protrusion morphology observed in the control cells. This phenomenon arises as a direct consequence of the impaired Egfr-pERK-Epb41l2 signaling axis, leading to delayed crosstalk between astrocytes and neurons. This delay results in reduced neuronal dendritic complexity and decreased neuronal excitability (due to damage to the Sema6a-Plxna2/4 receptor pair between astrocytes and neurons during the critical period), ultimately leading to the manifestation of depressive-like behaviors in adult mice.
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Project description:Neural functions and circuit establishment are characterized by intricate crosstalk among multiple cell types during critical periods. Impeding or delaying the crosstalk results in abnormal neural functions and neurodevelopmental disorders. However, the lack of robust mouse models to study the crosstalk between astrocytes and neurons thus renders unclear the implications of impeding such interactions. Here we found that Egfr knockout led to the absence of astrocytes during the critical period of neuronal maturation, with recovery observed in adult mice, providing an exceptional opportunity to investigate the consequences of delaying crosstalk between astrocytes and neurons. We show that, in the absence of Egfr, glial progenitor cells are unable to migrate outwardly, exhibiting a rounded and smooth morphology. This phenomenon arises as a direct consequence of the impaired Egfr-pERK-Epb41l2 signaling axis, leading to delayed communication between astrocytes and neurons. This delay results in reduced neuronal dendritic complexity and decreased neuronal excitability (due to damage to the Sema6a-Plxna2/4 receptor pair between astrocytes and neurons during the critical period), ultimately leading to the manifestation of depressive-like behaviors in adult mice.
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