Huntingtin is required for ciliogenesis and neurogenesis during early Xenopus development

Abstract

Huntington's Disease (HD) is a neurodegenerative disorder that results from the abnormal expansion of poly-glutamine (polyQ) repeats in the Huntingtin (HTT) gene. Although HTT has been linked to a variety of cellular events, it is still not clear what the physiological functions of the protein are. Because of its critical role during mouse embryonic mouse development, we investigated the functions of Htt during early Xenopus embryogenesis. We find that reduction of Htt levels affects cilia polarity and function and causes whole body paralysis. Moreover, Htt loss of function leads to abnormal development of trigeminal and motor neurons. Interestingly, these phenotypes are partially rescued by either wild-type or expanded HTT. These results show that the Htt activity is required for normal embryonic development, and highlight the usefulness of the Xenopus system for investigating proteins involved in human diseases.

Keywords: Ciliogenesis; Huntingtin; Huntington's disease; Multiciliated cells; Neurogenesis; Xenopus.