title: 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.
authors.affiliation: The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Haremaki
authors.affiliation: The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
authors.forename: Alessia
authors.initials: A
authors.lastname: Deglincerti
authors.affiliation: The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States. Electronic address: brvnlou@rockefeller.edu.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Brivanlou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology; D002923:Cilia / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D000071058:Huntingtin Protein; D051379:Mice; D023421:Models, Animal; D008959:Models, Neurological; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D060172:Morpholinos; D009419:Nerve Tissue Proteins; D029867:Xenopus Proteins
keywords: Ciliogenesis; Huntingtin; Huntington's disease; Multiciliated cells; Neurogenesis; Xenopus