Regulation of Fasciclin II and synaptic terminal development by the splicing factor beag

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Alternative splicing of pre-mRNA generates synaptic protein diversity, but regulatory factors remain largely unknown.
• Synaptic development and function rely on precise control over protein isoforms.

Purpose of the Study:

• To identify novel factors regulating synaptic development through Drosophila mutagenesis screens.
• To investigate the role of identified genes in alternative splicing and synaptic morphology.

Main Methods:

• Conducted a genetic screen in Drosophila to identify mutants with aberrant synaptic development.
• Characterized the beag and dsmu1 genes, identifying beag as a spliceosomal protein.
• Analyzed synaptic levels of Fasciclin II (FasII) splice isoforms in mutant backgrounds.
• Performed rescue experiments by restoring specific FasII isoforms in beag mutants.

Main Results:

• Identified the beag gene, encoding a spliceosomal protein, in mutants with reduced synaptic boutons and neurotransmitter release.
• Demonstrated that beag and dsmu1 mutants exhibit altered synaptic levels of specific FasII splice isoforms.
• Showed that restoring a particular FasII isoform rescues synaptic morphology in beag mutants, indicating isoform-specific functions.
• Confirmed that this FasII isoform has unique roles in synaptic development beyond transsynaptic adhesion.

Conclusions:

• beag and dsmu1 are essential, previously uncharacterized splicing factors involved in regulating synapse development and function.
• Alternative splicing of FasII, controlled by these factors, is critical for establishing proper synaptic architecture and connectivity.
• Specific FasII isoforms play distinct roles in synaptic development, independent of their roles in cell adhesion.