Huntington's disease alters human neurodevelopment

被引：206

作者：

Barnat, Monia ^{[1
]}

Capizzi, Mariacristina ^{[1
]}

Aparicio, Esther ^{[1
]}

Boluda, Susana ^{[2
]}

Wennagel, Doris ^{[1
]}

Kacher, Radhia ^{[1
]}

Kassem, Rayane ^{[1
]}

Lenoir, Sophie ^{[1
]}

Agasse, Fabienne ^{[1
]}

Braz, Barbara Y. ^{[1
]}

Liu, Jeh-Ping ^{[3
]}

Ighil, Julien ^{[4
]}

Tessier, Aude ^{[5
]}

Zeitlin, Scott O. ^{[3
]}

Duyckaerts, Charles ^{[2
]}

Dommergues, Marc ^{[4
]}

Durr, Alexandra ^{[6
]}

Humbert, Sandrine ^{[1
]}

机构：

[1] Univ Grenoble Alpes, Grenoble Inst Neurosci, INSERM, U1216, Grenoble, France

[2] Pitie Salpetriere Univ Hosp, AP HP, Dept Neuropathol Raymond Escourolle, Paris, France

[3] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA

[4] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, Serv Gynecol Obstet, Paris, France

[5] Hop Necker Enfants Malad, AP HP, Unite Embryofoetopathol, Paris, France

[6] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, CNRS,INSERM,Paris Brain Inst,UMR7225,U1127, Paris, France

来源：

SCIENCE | 2020年 / 369卷 / 6505期

关键词：

CELL BIOLOGY; DIVISION; REVEALS; NETWORK; RESCUE;

D O I：

10.1126/science.aax3338

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 carried 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.

引用

页码：787 / +

页数：24

共 40 条

[1] Neural Progenitor Cell Polarity and Cortical Development [J].