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Huntington's disease alters human neurodevelopment.

Monia Barnat1, Mariacristina Capizzi1, Esther Aparicio1

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Huntington's disease, a neurodegenerative disorder, shows early neurodevelopmental abnormalities. Researchers found defects in fetal brain tissue, indicating the disease impacts development from early stages.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Huntington's disease is typically considered a late-manifesting neurodegenerative disorder.
  • Emerging evidence from mouse models and neuroimaging suggests potential neurodevelopmental impacts.

Purpose of the Study:

  • To investigate whether Huntington's disease affects neurodevelopment by examining fetal human and mouse tissues.

Main Methods:

  • Analysis of fetal human (13 weeks gestation) and mouse embryo tissues carrying the Huntington's disease mutation.
  • Microscopic examination for cellular and protein abnormalities.
  • Investigation of progenitor cell behavior, including migration and differentiation.

Main Results:

  • Observed mislocalization of mutant huntingtin and junctional complex proteins in developing human cortical tissue.
  • Identified defects in neuroprogenitor cell polarity, differentiation, ciliogenesis, mitosis, and cell cycle progression in both human and mouse models.
  • Linked these abnormalities in mouse embryos to impaired interkinetic nuclear migration of progenitor cells.

Conclusions:

  • Huntington's disease possesses a significant neurodevelopmental component.
  • The disease pathology begins during early development, not solely as a degenerative process later in life.