title: vhnf1 and Fgf signals synergize to specify rhombomere identity in the zebrafish hindbrain.
abstract: Vertebrate hindbrain segmentation is a highly conserved process but the mechanism of rhombomere determination is not well understood. Recent work in the zebrafish has shown a requirement for fibroblast growth factor (Fgf) signaling and for the transcription factor variant hepatocyte nuclear factor 1 (vhnf1) in specification of rhombomeres 5 and 6 (r5+r6). We show here that vhnf1 functions in two ways to subdivide the zebrafish caudal hindbrain domain (r4-r7) into individual rhombomeres. First, vhnf1 promotes r5+r6 identity through an obligate synergy with Fgf signals to activate valentino and krox20 expression. Second, vhnf1 functions independently of Fgf signals to repress hoxb1a expression. Although vhnf1 is expressed in a broad posterior domain during gastrulation, it promotes the specification of individual rhombomeres. This is achieved in part because vhnf1 gives cellular competence to respond to Fgf signals in a caudal hindbrain-specific manner.
authors.affiliation: Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Wiellette
authors.forename: Hazel
authors.initials: H
authors.lastname: Sive
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051539:Hepatocyte Nuclear Factor 1-beta; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D051258:MafB Transcription Factor; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins
chemical_list: D004268:DNA-Binding Proteins; C101121:HOXB1 homeodomain protein; C068755:Hnf1b protein, rat; D018398:Homeodomain Proteins; D051258:MafB Transcription Factor; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D029961:Zebrafish Proteins; C111092:mafb protein, zebrafish; D051539:Hepatocyte Nuclear Factor 1-beta; D005346:Fibroblast Growth Factors