TY - JOUR
T1 - Genetic interactions in zebrafish midline development
AU - Halpern, Marnie E.
AU - Hatta, Kohei
AU - Amacher, Sharon L.
AU - Talbot, William S.
AU - Yan, Yi Lin
AU - Thisse, Bernard
AU - Thisse, Christine
AU - Postlethwait, John H.
AU - Kimmel, Charles B.
N1 - Funding Information:
We thank Bess Melby and Rachel Warga for allowing us to cite their unpublished data, Bob Riggleman and Phil Ingham for providing us with probes, and Steve Farber and Tammy Wu for their help in data analysis. Tammy Wu also supplied the photographs for Fig. 1. Ruth BreMiller and Mike Sepanski prepared sectioned material and Elaina Lawson, Bonnie Ullmann, Charline Walker, and Mike Frontzak provided additional technical assistance. We thank Bruce Bowerman, Bruce Draper, and many of our colleagues in the Institute of Neuroscience for critically reading drafts. This study was supported by an MRC Centennial Fellowship (M.E.H.), an American Cancer Society Fellowship (S.L.A.), a Jane Cof®n Childs Fellowship (W.S.T.), an EMBO Fellowship (C.T.), a Fogarty Fellowship (B.T.), by the Institut National de la Sante et de la Recherche MeÂdi-cale, the CNRS and the Centre Hospitalier Universitaire ReÂgional (C.T. and B.T.), and by NIH Grants NS17963 (C.B.K.), 1RO1AI26734 and 1RO1RR10715 (J.H.P.), and HD22486 (C.B.K. and J.H.P.)
PY - 1997/7/15
Y1 - 1997/7/15
N2 - Mutational analyses have shown that the genes no tail (nt1, 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 nt1 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;nt1 double mutants are not additive, but are most often similar to those in nt1 single mutants. This finding reveals that loss of nt1 function can suppress phenotypic defects due to mutation at flh, and we interpret it to mean that the wild-type allele of nt1 (nt1+) functions upstream to flh in a regulatory hierarchy. Loss of function of nt1 also strongly suppresses the floor plate deficiency in cyc mutants, for we found trunk floor plate to be present in cyc;nt1 double mutants. From these findings we propose that nt1+ plays an early role in cell fate choice at the dorsal midline, mediated by the Nt1 protein acting to antagonize floor plate development as well as to promote notochord development.
AB - Mutational analyses have shown that the genes no tail (nt1, 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 nt1 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;nt1 double mutants are not additive, but are most often similar to those in nt1 single mutants. This finding reveals that loss of nt1 function can suppress phenotypic defects due to mutation at flh, and we interpret it to mean that the wild-type allele of nt1 (nt1+) functions upstream to flh in a regulatory hierarchy. Loss of function of nt1 also strongly suppresses the floor plate deficiency in cyc mutants, for we found trunk floor plate to be present in cyc;nt1 double mutants. From these findings we propose that nt1+ plays an early role in cell fate choice at the dorsal midline, mediated by the Nt1 protein acting to antagonize floor plate development as well as to promote notochord development.
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U2 - 10.1006/dbio.1997.8605
DO - 10.1006/dbio.1997.8605
M3 - Article
C2 - 9242414
AN - SCOPUS:0030804983
VL - 187
SP - 154
EP - 170
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 2
ER -