title: Genetic interactions in zebrafish midline development.
abstract: Mutational analyses have shown that the genes no tail (ntl, Brachyury homolog), floating head (flh, a Not homeobox gene), and cyclops (cyc) play direct and essential roles in the development of midline structures in the zebrafish. In both ntl and flh mutants a notochord does not develop, and in cyc mutants the floor plate is nearly entirely missing. We made double mutants to learn how these genes might interact. Midline development is disrupted to a greater extent in cyc;flh double mutants than in either cyc or flh single mutants; their effects appear additive. Both the notochord and floor plate are completely lacking, and other phenotypic disturbances suggest that midline signaling functions are severely reduced. On the other hand, trunk midline defects in flh;ntl double mutants are not additive, but are most often similar to those in ntl single mutants. This finding reveals that loss of ntl function can suppress phenotypic defects due to mutation at flh, and we interpret it to mean that the wild-type allele of ntl (ntl+) functions upstream to flh in a regulatory hierarchy. Loss of function of ntl also strongly suppresses the floor plate deficiency in cyc mutants, for we found trunk floor plate to be present in cyc;ntl double mutants. From these findings we propose that ntl+ plays an early role in cell fate choice at the dorsal midline, mediated by the Ntl protein acting to antagonize floor plate development as well as to promote notochord development.
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene 97403-1254, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Halpern
authors.forename: K
authors.initials: K
authors.lastname: Hatta
authors.forename: S L
authors.initials: SL
authors.lastname: Amacher
authors.forename: W S
authors.initials: WS
authors.lastname: Talbot
authors.forename: Y L
authors.initials: YL
authors.lastname: Yan
authors.forename: B
authors.initials: B
authors.lastname: Thisse
authors.forename: C
authors.initials: C
authors.lastname: Thisse
authors.forename: J H
authors.initials: JH
authors.lastname: Postlethwait
authors.forename: C B
authors.initials: CB
authors.lastname: Kimmel
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics*; D047108:Embryonic Development; D004627:Embryonic Induction / Q000235:genetics*; D004843:Epistasis, Genetic; D005326:Fetal Proteins / Q000235:genetics*; D016153:Genes, Suppressor; D018398:Homeodomain Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008954:Models, Biological; D009154:Mutation; D009672:Notochord / Q000196:embryology; D010940:Plant Proteins / Q000235:genetics*; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins; D000098908:Brachyury Protein
chemical_list: D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D018398:Homeodomain Proteins; D010940:Plant Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000098908:Brachyury Protein; C101995:cycloidea protein, Antirrhinum; C096660:noto protein, zebrafish