Drosophila WDFY3/Bchs overexpression impairs neural function.

Area of Science:

• Neuroscience
• Genetics
• Cell Biology

Background:

• Pathogenic variants in WDFY3 are linked to neurodevelopmental disorders.
• WDFY3 encodes the autophagy adaptor protein ALFY.
• The effects of WDFY3 upregulation in the central nervous system (CNS) are largely unknown.

Purpose of the Study:

• To investigate the consequences of WDFY3 ortholog (Bchs) upregulation in Drosophila glial and neuronal cells.
• To understand the impact of Bchs overexpression on autophagy, locomotion, and overall morphology.
• To identify genes and pathways affected by Bchs upregulation in different cell types.

Main Methods:

• Overexpression of the Drosophila WDFY3 ortholog, Bchs, in glial and neuronal cells.
• Assessment of autophagy and locomotion.
• Analysis of ventral nerve cord (VNC) size and glial nuclei number.
• Gene expression profiling to identify differentially expressed genes.
• Gene Ontology (GO) analysis of affected genes.

Main Results:

• Glial or neuronal Bchs overexpression impaired autophagy and locomotion.
• Glial Bchs overexpression increased VNC size and glial nuclei number.
• Neuronal Bchs overexpression affected wing and thorax morphology.
• 79 differentially expressed genes overlapped between glial and neuronal Bchs overexpression.
• Neuronal Bchs overexpression led to differential gene expression in autophagy and mitochondrial function categories.

Conclusions:

• WDFY3 (Bchs) upregulation in either glial or neuronal cells has detrimental effects on neural function.
• Both cell types show impaired autophagy and locomotion upon Bchs upregulation.
• Glial and neuronal Bchs upregulation impact distinct developmental and cellular processes.
• Gene expression analysis reveals conserved and cell-specific responses to WDFY3 upregulation.