title: New Otx2 mRNA isoforms expressed in the mouse brain.
abstract: The mouse Otx2 gene is essential throughout head and brain development, from anterior-posterior polarity determination and neuroectoderm induction to post-natal sensory organ maturation. These numerous activities must rely on a very finely tuned regulation of expression. In order to understand the molecular control of the Otx2 gene, we set out to isolate its promoter. During this quest, we identified three remote transcription start sites, two defining two new upstream exons and one mapping within the previously reported first exon. The three transcripts differed in their 5' non-coding region but encoded the same protein. The transcription start nucleotides of each mRNA species have been mapped by RNase protection assays and by an RNA circularization technique. We have demonstrated that they are all used and linked to functional promoters. In addition to leader versatility, we also detected alternative splicing within the coding sequence that gives rise to a new protein endowed with an 8 amino-acid insertion upstream of the homeodomain. Combined analysis of the relative abundance of Otx2 mRNA isoforms in representative tissues and in situ hybridization studies revealed distinct spatial and temporal, although partially overlapping, expression patterns of the mRNA isoforms. These findings provide new clues to a better understanding of the relationships between Otx2 gene architecture and its complex regulatory requirements.
authors.affiliation: LBMC, ENS-Lyon, 46 allée d'Italie, 69364 Lyon cedex 07, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Courtois
authors.forename: Gilles
authors.initials: G
authors.lastname: Chatelain
authors.forename: Zhi-Yan
authors.initials: ZY
authors.lastname: Han
authors.forename: Nicolas
authors.initials: N
authors.lastname: Le Novère
authors.forename: Gilbert
authors.initials: G
authors.lastname: Brun
authors.forename: Thomas
authors.initials: T
authors.lastname: Lamonerie
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D005091:Exons / Q000235:genetics; D018398:Homeodomain Proteins; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009928:Organ Specificity; D051857:Otx Transcription Factors; D011149:Pons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D012160:Retina / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D024363:Transcription Initiation Site
chemical_list: D020121:5' Untranslated Regions; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D015534:Trans-Activators