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Development. 2018 Jan 3;145(1). pii: dev154047. doi: 10.1242/dev.154047.

Shep regulates Drosophila neuronal remodeling by controlling transcription of its chromatin targets.

Author information

1
Nuclear Organization and Gene Expression Section, Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2
Nuclear Organization and Gene Expression Section, Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA leielissa@niddk.nih.gov.

Abstract

Neuronal remodeling is crucial for formation of the mature nervous system and disruption of this process can lead to neuropsychiatric diseases. Global gene expression changes in neurons during remodeling as well as the factors that regulate these changes remain poorly defined. To elucidate this process, we performed RNA-seq on isolated Drosophila larval and pupal neurons and found upregulated synaptic signaling and downregulated gene expression regulators as a result of normal neuronal metamorphosis. We further tested the role of alan shepard (shep), which encodes an evolutionarily conserved RNA-binding protein required for proper neuronal remodeling. Depletion of shep in neurons prevents the execution of metamorphic gene expression patterns, and shep-regulated genes correspond to Shep chromatin and/or RNA-binding targets. Reduced expression of a Shep-inhibited target gene that we identified, brat, is sufficient to rescue neuronal remodeling defects of shep knockdown flies. Our results reveal direct regulation of transcriptional programs by Shep to regulate neuronal remodeling during metamorphosis.

KEYWORDS:

BMP signaling; Chromatin insulator; Metamorphosis; Neuronal remodeling; Neuronal transcriptome; shep

PMID:
29158441
PMCID:
PMC5825876
DOI:
10.1242/dev.154047
[Indexed for MEDLINE]
Free PMC Article

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