RRC ID 57366
Author Li JSS, Millard SS.
Title Deterministic splicing of Dscam2 is regulated by Muscleblind.
Journal Sci Adv
Abstract Alternative splicing increases the proteome diversity crucial for establishing the complex circuitry between trillions of neurons. To provide individual cells with different repertoires of protein isoforms, however, this process must be regulated. Previously, we found that the mutually exclusive alternative splicing of Drosophila Dscam2 produces two isoforms (A and B) with unique binding properties. This splicing event is cell type specific, and the transmembrane proteins that it generates are crucial for the development of axons, dendrites, and synapses. Here, we show that Muscleblind (Mbl) controls Dscam2 alternative splicing. Mbl represses isoform A and promotes the selection of isoform B. Mbl mutants exhibit phenotypes also observed in flies engineered to express a single Dscam2 isoform. Consistent with this, mbl expression is cell type specific and correlates with the splicing of isoform B. Our study demonstrates how the regulated expression of a splicing factor is sufficient to provide neurons with unique protein isoforms crucial for development.
Volume 5(1)
Pages eaav1678
Published 2019-1-1
DOI 10.1126/sciadv.aav1678
PII aav1678
PMID 30746474
PMC PMC6357765
MeSH Alternative Splicing* Animals Animals, Genetically Modified Drosophila Proteins / genetics* Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Exons Gene Expression Regulation Mushroom Bodies / cytology Mushroom Bodies / physiology Mutation Neural Cell Adhesion Molecules / genetics* Neural Cell Adhesion Molecules / metabolism Neurons / physiology Nuclear Proteins / genetics Nuclear Proteins / metabolism* RNA Interference
IF 12.804
Times Cited 2