A new study in zebrafish reveals that the gene nexmifb—a paralog of the human neurodevelopmental gene NEXMIF—plays a critical role in spinal motor neuron development by modulating the axon guidance molecule efna5b.
Using whole-mount in situ hybridization, researchers first showed that nexmifb is expressed in the brain and spinal cord of zebrafish embryos. Knockdown of nexmifb via morpholino oligonucleotides led to shortened body length, significant loss of primary motor neurons, and reduced axonal length and branching in caudal primary motor neurons. TUNEL assays indicated that motor neuron loss was not attributable to apoptosis, pointing to alternative mechanisms.
Transcriptomic profiling revealed hundreds of differentially expressed genes between nexmifb morphants and controls. Among downregulated genes, efna5b—an ephrin family member involved in axon guidance—showed the most pronounced reduction. Importantly, co-injection of efna5b mRNA partially rescued the motor neuron defects caused by nexmifb knockdown, restoring axonal length and branching.
These findings position nexmifb as a key regulator of motor neuron development and suggest that it acts, at least in part, through efna5b. The work provides new insights into the molecular mechanisms underlying motor neuron development and offers potential avenues for understanding related neurological disorders. The research, entitled “The Role of Nexmifb in Regulating Spinal Motor Neuron Development through Efna5b in Zebrafish” was published in Translational Neurology and Neurosurgery (Volume 1, Issue 1, 2026)
DOI：10.2738/TNN.2026.0003