title: Molecular dissection of segment formation in the developing hindbrain.
abstract: Although many components of the genetic pathways that provide positional information during embryogenesis have been identified, it remains unclear how these signals are integrated to specify discrete tissue territories. Here, we investigate the molecular mechanisms underlying the formation of one of the hindbrain segments, rhombomere (r) 3, specified by the expression of the gene krox20. Dissecting krox20 transcriptional regulation has identified several input pathways: Hox paralogous 1 (PG1) factors, which both directly activate krox20 and indirectly repress it via Nlz factors, and the molecular components of an Fgf-dependent effector pathway. These different inputs are channelled through a single initiator enhancer element to shape krox20 initial transcriptional response: Hox PG1 and Nlz factors define the anterior-posterior extent of the enhancer's domain of activity, whereas Fgf signalling modulates the magnitude of activity in a spatially uniform manner. Final positioning of r3 boundaries requires interpretation of this initial pattern by a krox20 positive-feedback loop, orchestrated by another enhancer. Overall, this study shows how positional information provided by different patterning mechanisms is integrated through a gene regulatory network involving two cis-acting elements operating on the same gene, thus offering a comprehensive view of the delimitation of a territory.
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris F-75005, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Labalette
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IFD, 4 Place Jussieu, Paris 75252, Cedex 05, France.
authors.forename: Michel Adam
authors.initials: MA
authors.lastname: Wassef
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris F-75005, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Desmarquet-Trin Dinh
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IFD, 4 Place Jussieu, Paris 75252, Cedex 05, France.
authors.forename: Yassine Xavier
authors.initials: YX
authors.lastname: Bouchoucha
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IFD, 4 Place Jussieu, Paris 75252, Cedex 05, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Le Men
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris F-75005, France patrick.charnay@ens.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Charnay
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris F-75005, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Gilardi-Hebenstreit
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins
keywords: Egr2; Fgf; Hox; Krox20; Nlz; Rhombomere; Segmentation; Transcriptional enhancer; Zebrafish