Huntington's disease: brain abnormalities detectable as early as the embryonic stage

Published July 17 2020
Coupe de cerveau humain (cortex). A gauche, les noyaux sont marqués en bleu; à droite le cil qui est présent au pied apical (en vert) des cellules progénitrices est marqué en rouge. La surface apicale est marquée en bleu. © Monia Barnat/Grenoble Institut des Neurosciences/Inserm, Université Grenoble Alpes

Section of human brain (cortex). On the left, the nuclei are marked in blue; on the right, the cilium at the apical foot (in green) of the progenitor cells is marked in red. The apical surface is marked in blue.
© Monia Barnat/Grenoble Institut des Neurosciences/Inserm, Université Grenoble Alpes

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Although Huntington’s disease is a late-manifesting neurodegenerative disorder, both mouse studies and neuroimaging studies of presymptomatic mutation carriers suggest that Huntington’s disease might affect neurodevelopment. To determine whether this is actually the case, we examined tissue from human fetuses (13 weeks gestation) that carry the Huntington’s disease mutation. These tissues showed clear abnormalities in the developing cortex, including mislocalization of mutant huntingtin and junctional complex proteins, defects in neuroprogenitor cell polarity and differentiation, abnormal ciliogenesis, and changes in mitosis and cell cycle progression. We observed the same phenomena in Huntington’s disease mouse embryos, where we linked these abnormalities to defects in interkinetic nuclear migration of progenitor cells. Huntington’s disease thus has a neurodevelopmental component and is not solely a degenerative disease.

Sources :

Huntington disease alters human neurodevelopment

Scientific teams

Team "Basic to translational neurogenetics"
Team leader
Alexandra DURR MD, PhD, PU-PH, Sorbonne university-AP-HP
Giovanni STEVANIN PhD, DR2, PU, INSERM/EPHE
Physiopathology of neurological disorders
Main domain : Cellular & molecular neurosciences
Subdomain : Clinical & translational neurosciences

Alexandra DURR & Giovanni STEVANIN’s team focus on two groups of neurogenetic diseases, spinocerebellar degenerations – SCD (spastic paraplegias and cerebellar ataxias) and frontotemporal lobar degenerations – FTLD. These rare conditions share clinical, genetic and functional characteristics, such as motor neuron dysfunction but are extremely heterogeneous both in molecular and clinical aspects.
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