BRCA1 and ELK-1 regulate Neural Progenitor Cell Fate in the Optic Tectum in response to Visual Experience in Xenopus laevis tadpoles
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA763977 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15926817.fastq.gz | Fastqsanger.gz | |||
| SRR15926818.fastq.gz | Fastqsanger.gz | |||
| SRR15926819.fastq.gz | Fastqsanger.gz | |||
| SRR15926820.fastq.gz | Fastqsanger.gz | |||
| SRR15926821.fastq.gz | Fastqsanger.gz |
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Project description:To identify regulators of activity-dependent neural progenitor cell fate, we used RNA-Seq to profile the transcriptomes of proliferating neural progenitor cells and newly-differentiated immature neurons. We identified six DE transcription factors which are predicted to regulate the majority of the other DE transcripts. We investigated the effect of BRCA1 and ELK-1 on activity-regulated neurogenesis in the tadpole visual system and found that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells, and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 expression, while the effects of visual experience on neuronal differentiation depend on ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.
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Project description:Sensory experience influences the establishment of neural connectivity through molecular mechanisms that remain unclear. Here, we employ single-nucleus RNA-sequencing to investigate the contribution of sensory-driven gene expression to synaptic refinement in the dorsal lateral geniculate nucleus of the thalamus, a region of the brain that processes visual information. We find that visual experience induces the expression of the cytokine receptor Fn14 in excitatory thalamocortical neurons. By combining electrophysiological and structural techniques, we show that Fn14 is dispensable for early phases of refinement mediated by spontaneous activity, but that Fn14 is essential for refinement during a later, experience-dependent period of development. Refinement deficits in mice lacking Fn14 are associated with functionally weaker and structurally smaller retinogeniculate inputs, indicating that Fn14 mediates both functional and anatomical rearrangements in response to sensory experience. These findings identify Fn14 as a molecular link between sensory-driven gene expression and vision-sensitive refinement in the brain.
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Project description:In developing Xenopus tadpoles, the optic tectum begins to receive patterned visual input while visuomotor circuits are still undergoing neurogenesis and circuit assembly. This visual input regulates neural progenitor cell fate decisions such that maintaining tadpoles in the dark increases proliferation, expanding the progenitor pool, while visual stimulation promotes neuronal differentiation. To identify regulators of activity-dependent neural progenitor cell fate, we profiled the transcriptomes of proliferating neural progenitor cells and newly differentiated neurons using RNA-Seq. We used advanced bioinformatic analysis of 1,130 differentially expressed transcripts to identify six differentially regulated transcriptional regulators, including Breast Cancer 1 (BRCA1) and the ETS-family transcription factor, ELK-1, which are predicted to regulate the majority of the other differentially expressed transcripts. BRCA1 is known for its role in cancers, but relatively little is known about its potential role in regulating neural progenitor cell fate. ELK-1 is a multifunctional transcription factor which regulates immediate early gene expression. We investigated the potential functions of BRCA1 and ELK-1 in activity-regulated neurogenesis in the tadpole visual system using in vivo time-lapse imaging to monitor the fate of GFP-expressing SOX2+ neural progenitor cells in the optic tectum. Our longitudinal in vivo imaging analysis showed that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 and ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.
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