Authors
Takakazu Yokokura, Hansine Heggeness, Seiko Yoshikawa, Salvatore Alaimo, Thirada Boonrawd, Navpreet Ahluwalia, Thi Thu Van Dihn, Alfredo Ferro, Elizabeth M McNeill, David Van Vactor
Published in
Human molecular genetics. Volume 35. Issue 20. Sep 11, 2026.
Abstract
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder associated with motor neuron degeneration, yet the role of the well-conserved Survival of Motor Neuron (SMN) protein in muscle remains insufficiently understood. Using the Drosophila neuromuscular junction (NMJ) as a model, we combined tissue-specific Smn depletion with transcriptomic profiling and prior genetic modifier screens to identify SMN-dependent genes that contribute to synaptic architecture. Functional screening of candidate genes significantly and selectively effected in muscle identified genes whose knockdown phenocopied NMJ morphometry defects characteristic of Smn loss-of-function (LOF), including FER, CAP, HDAC4, Nhe2, and Raskol. Unlike other genes in this group, analysis of postsynaptic architecture using a subsynaptic reticulum (SSR) biomarker disrupted by Smn LOF singled out the conserved tyrosine kinase FER as an SMN-dependent gene in muscle that influences this prominent feature of the NMJ. Analysis of different FER transcripts suggests that elevation of the FERp100 protein isoform in Smn LOF muscle tissue leads to a dominant-negative effect likely to disrupt signaling via the MAPK-family kinase Basket (Bsk) to regulate the downstream phosphatase Puckered (Puc).
PMID:
42804671
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.
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