SMA Research Platform

Cross-Species Splicing Map

EXPLORATORY

Axolotl and zebrafish use alternative splicing as a master switch for regeneration. The same genes exist in humans but their regeneration-promoting isoforms are epigenetically silenced. This module maps regeneration-specific splice events to human orthologs.

▶How does conservation and feasibility scoring work?

Why can axolotls regenerate limbs? The axolotl (Ambystoma mexicanum) and zebrafish (Danio rerio) switch on alternative mRNA isoforms during injury that activate cell proliferation, cytoskeletal remodeling, and axon re-growth programs. These isoforms are encoded in the same genes humans carry — but in us they are epigenetically silenced after embryonic development.

Conservation measures sequence identity between species (≥ 0.8 = highly conserved, likely functional in humans). Feasibility estimates ASO targeting potential (exon accessibility, splice site strength, existing ASO precedent). Events with high conservation + high feasibility are the strongest candidates for therapeutic reactivation. Nusinersen (Spinraza) proves that ASO-mediated splice switching works for SMA.

Connection to SMN2 exon 7: Nusinersen (Spinraza) proves that ASO-mediated splice switching works for SMA. The same approach could reactivate regeneration-promoting isoforms in genes like ctnnb1 (Wnt pathway),fgf signaling, and cytoskeletal remodelers — giving motor neurons tools to repair rather than just survive. By mapping which exons are alternatively spliced in regenerating animals vs. human SMA motor neurons, we identify candidate ASO targets that could reawaken these dormant programs.

Loading splice events…