Fiche publication
Date publication
novembre 2018
Journal
Human molecular genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Mme MESSADDEQ Nadia
Tous les auteurs :
Carrillo-Rosas S, Weber C, Fievet L, Messaddeq N, Karam A, Trottier Y
Lien Pubmed
Résumé
Polyglutamine expansion in Ataxin-7 results in Spinocerebellar ataxia type 7 (SCA7) and causes visual impairment. SCA7 photoreceptors progressively lose their outer segments, a structure essential for their visual function. Ataxin-7 is a subunit of the transcriptional coactivator Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex, implicated in the development of the visual system in flies. To determine the function of Ataxin-7 in the vertebrate eye, we have inactivated Ataxin-7 in zebrafish. While Ataxin-7 depletion in flies led to gross retinal degeneration, in zebrafish it primarily results in ocular coloboma, a structural malformation responsible for pediatric visual impairment in human. Ataxin-7 inactivation leads to elevated Hedgehog signaling in the forebrain, causing an alteration of proximo-distal patterning of the optic vesicle during early eye development and coloboma. At later developmental stages, malformations of photoreceptors due to incomplete formation of their outer segments are observed, and correlate with altered expression of crx, a key transcription factor involved in the formation of photoreceptor outer segment. Therefore, we propose that a primary toxic effect of polyglutamine expansion is the alteration of Ataxin-7 function in the daily renewal of outer segment in SCA7. Together, our data indicate that Ataxin-7 plays an essential role in vertebrate eye morphogenesis and photoreceptor differentiation, and its loss of function may contribute to the development of human coloboma.
Référence
Hum. Mol. Genet.. 2018 Nov 16;:
