Huntingtin as a cytoskeletal organizer for callosal fibers wiring
Mariacristina CAPIZZI
Team NeuroGen, ICM Paris

Abstract
Huntington’s disease (HD) is an adult-onset neurodegenerative disorder with a silent phase associated with brain development. Beyond its well-known striatal vulnerability, HD reveals that callosal fibers dysfunction emerges decades before the onset of symptoms, indicating a neurodevelopmental origin. In this seminar, I will discuss how cytoskeletal disorganization alters axonal growth and pathfinding of callosal neurons in HD mouse models. These processes are essential for the assembly of functional cortical connections in the brain. Using HD as a model, our study uncovered the physiological role of huntingtin (HTT) as a cytoskeletal organizer that bundles F-actin, stabilizes growth cone architecture, and coordinates its molecular composition. In HD, partial loss of these functions disrupts actin–microtubule organization, impairing the growth and guidance of callosal axons. This developmental miswiring may compromise cortical connectivity and function. Altogether, I propose that HD constitutes a powerful system for dissecting the molecular logic of circuit formation and exploring early interventions targeting cytoskeleton-dependent wiring precision.

Invited by T. Marissal and E. Fino

Monday 4 May 2026 at 11am – Inmed Conference Room