Stathmin-2 regulates microtubule dynamics and axonal resilience in human motor neurons

STMN2 depletion in human induced pluripotent stem cell-derived motor neurons disrupts microtubule recovery after nocodazole-induced depolymerization and impairs axonal recoil after local severing.

• Why it matters: ALS involves selective motor neuron degeneration, but how STMN2—lost downstream of TDP-43 pathology in nearly all cases—supports cytoskeletal resilience is not well defined.
• What they did: Using TIRF microscopy, the study measured STMN2-dependent microtubule growth and catastrophe at single-microtubule resolution, then tested recovery after transient nocodazole depolymerization and axonal responses to optically induced severing.
• The result: STMN2 depletion increased baseline microtubule polymerization yet reduced post-stress microtubule recovery and axonal recoil, and it also disrupted neuromuscular junction-like contacts in human motor neuron–myocyte co-cultures.

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