title: Conserved and acquired features of neurogenin1 regulation.
abstract: The telencephalon shows vast morphological variations among different vertebrate groups. The transcription factor neurogenin1 (ngn1) controls neurogenesis in the mouse pallium and is also expressed in the dorsal telencephalon of the evolutionary distant zebrafish. The upstream regions of the zebrafish and mammalian ngn1 loci harbour several stretches of conserved sequences. Here, we show that the upstream region of zebrafish ngn1 is capable of faithfully recapitulating endogenous expression in the zebrafish and mouse telencephalon. A single conserved regulatory region is essential for dorsal telencephalic expression in the zebrafish, and for expression in the dorsal pallium of the mouse. However, a second conserved region that is inactive in the fish telencephalon is necessary for expression in the lateral pallium of mouse embryos. This regulatory region, which drives expression in the zebrafish diencephalon and hindbrain, is dependent on Pax6 activity and binds recombinant Pax6 in vitro. Thus, the regulatory elements of ngn1 appear to be conserved among vertebrates, with certain differences being incorporated in the utilisation of these enhancers, for the acquisition of more advanced features in amniotes. Our data provide evidence for the co-option of regulatory regions as a mechanism of evolutionary diversification of expression patterns, and suggest that an alteration in Pax6 expression was crucial in neocortex evolution.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries, 67404 Illkirch Cedex, CU de Strasbourg, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Blader
authors.forename: Chen Sok
authors.initials: CS
authors.lastname: Lam
authors.forename: Sepand
authors.initials: S
authors.lastname: Rastegar
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scardigli
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Nicod
authors.forename: Nicolas
authors.initials: N
authors.lastname: Simplicio
authors.forename: Charles
authors.initials: C
authors.lastname: Plessy
authors.forename: Nadine
authors.initials: N
authors.lastname: Fischer
authors.forename: Carol
authors.initials: C
authors.lastname: Schuurmans
authors.forename: François
authors.initials: F
authors.lastname: Guillemot
authors.forename: Uwe
authors.initials: U
authors.lastname: Strähle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D017124:Conserved Sequence / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009928:Organ Specificity; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012097:Repressor Proteins; D020218:Response Elements / Q000235:genetics; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism; D016415:Sequence Alignment; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse; C486337:neurog1 protein, zebrafish