Most of the interest in the huntingtin protein has centred on the fact that, when mutated, huntingtin causes Huntington’s disease (HD), a devastating neurodegenerative disorder. The mutation causing HD is an abnormal polyglutamine stretch in huntingtin. Since HD is characterised by the adult onset, the dysfunction and death of adult neurons, most studies have focused on the toxic effects elicited by mutant huntingtin in post-mitotic neurons. However, the protein is ubiquitous and expressed in the developing embryo where it plays an essential role as revealed by the early embryonic lethality at day 7.5 of the complete huntingtin knock-out mice. Anyway, the roles of the wild-type protein during development have been overlooked. Here, we investigated the role of huntingtin during cortical development. We used genetic mouse models and in utero electroporation to inactivate huntingtin in specific lineages. We found that huntingtin regulates several steps of mouse embryonic corticogenesis. We will also show the consequences of the presence of an abnormal polyglutamine expansion in huntingtin during cortical neurogenesis and consider the viewing of HD as a developmental disorder.
- cortical development
- mouse models