Proteomic profiling of Elp1-deficient trigeminal ganglia reveals disruption of neurotrophic and metabolic pathways in a familial dysautonomia mouse model.

BACKGROUND

Elp1, a subunit of the Elongator complex, is essential for tRNA modification and neuronal development. Mutations in ELP1 underlie familial dysautonomia (FD), a disorder marked by sensory and autonomic neuropathy. While loss of Elp1 disrupts trigeminal ganglion formation and survival, the downstream molecular consequences remain poorly defined.

RESULTS

We performed quantitative proteomic profiling of trigeminal ganglia from Elp1 conditional knockout (CKO) and control embryos at E13.5. Across 5650 detected proteins, 25 were significantly up-regulated and 26 down-regulated in Elp1 CKO embryos. EnrichR analysis revealed enrichment of up-regulated proteins in amino acid transport and tRNA aminoacylation pathways, with links to neuromuscular and neuropathic diseases. Down-regulated proteins were associated with RNA modification, cholesterol biosynthesis, and synaptic organization. Validation by immunohistochemistry confirmed decreased expression of the neurotrophic receptor Gfra3 and the neuropeptide Galanin, and increased levels of the chromatin regulator Chd1, in Elp1 CKO embryos relative to controls.

CONCLUSIONS

These findings demonstrate that Elp1 loss disrupts metabolic, RNA modification, and neurotrophic signaling pathways in the developing trigeminal ganglion. Proteomic analysis thus provides new insight into the molecular consequences of Elp1 deficiency and highlights candidate mechanisms contributing to sensory neuron vulnerability in FD.