Shared mechanisms between Drosophila peripheral nervous system development and human neurodegenerative diseases

- VAPB signaling at the NMJ is involved in the pathogenesis of ALS.
- PNS studies implicate a link between microRNA mediated genomic stability and ALS.
- A major mRNA splicing target of SMN in cholinergic neurons contributes to SMA.

Signaling pathways and cellular processes that regulate neural development are used post-developmentally for proper function and maintenance of the nervous system. Genes that have been studied in the context of the development of Drosophila peripheral nervous system (PNS) and neuromuscular junction (NMJ) have been identified as players in the pathogenesis of human neurodegenerative diseases, including spinocerebellar ataxia, amyotrophic lateral sclerosis, and spinal muscular atrophy. Hence, by unraveling the molecular mechanisms that underlie proneural induction, cell fate determination, axonal targeting, dendritic branching, and synapse formation in Drosophila, novel features related to these disorders have been revealed. In this review, we summarize and discuss how studies of Drosophila PNS and NMJ development have provided guidance in experimental approaches for these diseases.