Mutant huntingtin affects cortical progenitor cell division and development of the mouse neocortex

Molina-Calavita, Maria, Barnat, Monia, Elias, Salah, Aparicio, Esther, Piel, Matthieu and Humbert, Sandrine (2014) Mutant huntingtin affects cortical progenitor cell division and development of the mouse neocortex. Journal of Neuroscience, 34 (30), 10034-10040. (doi:10.1523/JNEUROSCI.0715-14.2014).

Abstract

A polyglutamine expansion in huntingtin (HTT) causes the specific death of adult neurons in Huntington's disease (HD). Most studies have thus focused on mutant HTT (mHTT) toxicity in adulthood, and its developmental effects have been largely overlooked. We found that mHTT caused mitotic spindle misorientation in cultured cells by altering the localization of dynein, NuMA, and the p150Glued subunit of dynactin to the spindle pole and cell cortex and of CLIP170 and p150Glued to microtubule plus-ends. mHTT also affected spindle orientation in dividing mouse cortical progenitors, altering the thickness of the developing cortex. The serine/threonine kinase Akt, which regulates HTT function, rescued the spindle misorientation caused by the mHTT, by serine 421 (S421) phosphorylation, in cultured cells and in mice. Thus, cortical development is affected in HD, and this early defect can be rescued by HTT phosphorylation at S421.

This record has no associated files available for download.

Contributors

Author: Salah Elias

Download statistics