PUBLICATION
srp54 promotes motor neuron development and is required for motility in zebrafish
- Authors
- Losievski, N., Kamath, P., Fox, A., Aloi, N.M., Baird, M.C., Everest, A., Gallagher, T.L., Amacher, S.L., Kolb, S.J.
- ID
- ZDB-PUB-250507-7
- Date
- 2025
- Source
- Neuroscience : (Journal)
- Registered Authors
- Amacher, Sharon, Gallagher, Thomas
- Keywords
- Central nervous system, Hatching gland, Neurodevelopment, Signal recognition particle, Spinal muscular atrophy
- MeSH Terms
-
- Animals, Genetically Modified
- Motor Neurons*/metabolism
- Motor Neurons*/physiology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Animals
- Zebrafish
- Axons/metabolism
- Axons/physiology
- Signal Recognition Particle*/genetics
- Signal Recognition Particle*/metabolism
- PubMed
- 40328346 Full text @ Neuroscience
Citation
Losievski, N., Kamath, P., Fox, A., Aloi, N.M., Baird, M.C., Everest, A., Gallagher, T.L., Amacher, S.L., Kolb, S.J. (2025) srp54 promotes motor neuron development and is required for motility in zebrafish. Neuroscience. :.
Abstract
The signal recognition particle (SRP) is a highly conserved ribonucleoprotein (RNP) that translocates a subset of secreted and integral membrane proteins to the endoplasmic reticulum for proper localization. The most conserved SRP protein component, SRP54, has been implicated in the molecular etiology of spinal muscular atrophy (SMA). A key feature of SMA is the selective loss of motor neurons; however, the mechanism underlying this selectivity is unknown. SMA arises from deficient levels of the ubiquitously expressed Survival of Motor Neuron (SMN) protein. SMN is proposed to assemble the SRP, and SMN deficiency in SMA may attenuate SRP function and contribute to motor neuron death in patients. Using zebrafish embryos homozygous for a srp54 nonsense mutation (srp54-/-), we investigated the requirement of Srp54 protein in motor axon development. The first grossly distinguishable phenotype observed in srp54-/- embryos was reduced motility at 30 h postfertilization (hpf). Additionally, we detected reduced length and branching of caudal primary motor axons in srp54-/- embryos compared to srp54+/+ and srp54+/- siblings at 30 hpf, suggesting that defective motor neurons may contribute to the observed immotility. We also examined additional neural, secretory, and migratory cell types at 30 hpf to assess whether motor neurons are especially vulnerable to Srp54 deficiency. Of the cell types evaluated, only the hatching gland had distinct expression pattern alterations in srp54-/- embryos at this developmental stage. Our findings suggest that Srp54 deficiency results in motor neuron developmental defects and support the hypothesis that SRP54 may influence motor neuron selectivity in SMA.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping