We are pleased to welcome Mariacristina Capizzi from the Paris Brain Institute, invited by Flavie Strappazzon.
She will give a seminar on April 23rd at 11:00 a.m. entitled:
“Huntingtin as a Regulator of Actin Architecture: Insights from Developing Cortical Circuits”
The seminar will take place in Amphi Hermann (1st floor) – Faculté de Médecine Lyon-Est Rockefeller.
Abstract
Huntington’s disease (HD) is a monogenic neurodegenerative disorder caused by a CAG expansion in the HTT gene. Although symptoms appear in adulthood, structural and functional abnormalities in the cortex and striatum emerge earlier, indicating a developmental contribution to HD pathogenesis.
Our work focuses on cortical projection neurons in layers V and II/III, which form corticostriatal and callosal circuits and rely on coordinated cytoskeletal dynamics and precise axonal guidance. These pathways provide a key framework for understanding connectivity alterations in HD.
We recently identified HTT as a direct actin-binding and actin-bundling protein. Loss of HTT leads to axonal growth defects and cytoskeletal disorganization, consistent with impaired growth cone architecture observed in HD. These findings motivate the exploration of axon guidance mechanisms that interface with cytoskeletal remodeling during circuit assembly in HD.
Understanding HTT’s cytoskeletal role shifts the field from viewing HTT solely through toxicity toward recognizing it as a multifunctional structural regulator whose loss of function may profoundly shape development, cellular physiology, and tissue integrity.
Selected Publications
- Capizzi M. et al. “Developmental defects in Huntington’s disease show that axonal growth and microtubule reorganization require NUMA1.” Neuron (2022)
- Barnat M., Capizzi M. et al. “Huntington’s disease alters human neurodevelopment.” Science (2020)
- Carpentier R., Kim J., Capizzi M.*@ et al. “Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization.” Science Advances (2025)