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Gene Review

noto  -  notochord homeobox

Danio rerio

Synonyms: SO:0000704, Znot, flh
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High impact information on flh

  • We propose that flh regulates notochord precursor cell fate [1].
  • This is in contrast to zebrafish embryos, in which flh interacts with ntl (zebrafish T) in a regulatory loop and is essential for development of the entire notochord, and suggests that different genetic control circuits act in different vertebrate species during notochord formation [2].
  • We show that mbl is required to prevent the expression of flh in dorsal forebrain cells rostral to the epiphysis [3].
  • In flh- embryos, the first few epiphysial neurons are generated, but beyond the 18 somite stage, neuronal production ceases [3].
  • In addition, a dominant-negative construct and antisense morpholino oligonucleotides led to a reduction in gsc and flh expression [4].

Biological context of flh


Anatomical context of flh

  • The homeodomain transcription factor Floating head (Flh) is required for the generation of neurones in the zebrafish epiphysis [8].
  • The midline mutants floating head (flh), sonic you (syu), and you-too (yot) provide the opportunity to study glomerular differentiation in the absence of the notochord and vascularization from the dorsal aorta [9].
  • In flh mutants, cells in the notochord domain generate clones of muscle cells [6].
  • A minority of cells in the notochord domain in wild-type embryos develop as unrestricted mesoderm, invariably located in the tail, suggesting that early gastrula expression of flh does not restrict cellular potential to the notochord fate [6].
  • In ntl mutants the spatial pattern of flh expression is altered as early as the late gastrula stage, becoming broad and diffuse [10].

Regulatory relationships of flh

  • In these mosaic embryos flh cells expressing flk assemble at the midline, beneath the wild-type notochord, and form an aortic primordium [11].
  • Expression of hsp90alpha is also activated in the midline of flh mutants when these cells switch from a notochord to a muscle fate [12].
  • floating head and masterblind regulate neuronal patterning in the roof of the forebrain [3].

Other interactions of flh

  • We show that ash1a and ngn1 function in parallel redundant pathways to regulate neurogenesis downstream of flh [8].
  • In contrast, the timing and morphology of otic development is not affected by mutations in no tail (ntl) or floating head (flh), which prevent notochord differentiation [13].


  1. A homeobox gene essential for zebrafish notochord development. Talbot, W.S., Trevarrow, B., Halpern, M.E., Melby, A.E., Farr, G., Postlethwait, J.H., Jowett, T., Kimmel, C.B., Kimelman, D. Nature (1995) [Pubmed]
  2. The mouse homeobox gene Not is required for caudal notochord development and affected by the truncate mutation. Abdelkhalek, H.B., Beckers, A., Schuster-Gossler, K., Pavlova, M.N., Burkhardt, H., Lickert, H., Rossant, J., Reinhardt, R., Schalkwyk, L.C., Müller, I., Herrmann, B.G., Ceolin, M., Rivera-Pomar, R., Gossler, A. Genes Dev. (2004) [Pubmed]
  3. floating head and masterblind regulate neuronal patterning in the roof of the forebrain. Masai, I., Heisenberg, C.P., Barth, K.A., Macdonald, R., Adamek, S., Wilson, S.W. Neuron (1997) [Pubmed]
  4. The maternally expressed zebrafish T-box gene eomesodermin regulates organizer formation. Bruce, A.E., Howley, C., Zhou, Y., Vickers, S.L., Silver, L.M., King, M.L., Ho, R.K. Development (2003) [Pubmed]
  5. Mutations affecting the formation of the notochord in the zebrafish, Danio rerio. Odenthal, J., Haffter, P., Vogelsang, E., Brand, M., van Eeden, F.J., Furutani-Seiki, M., Granato, M., Hammerschmidt, M., Heisenberg, C.P., Jiang, Y.J., Kane, D.A., Kelsh, R.N., Mullins, M.C., Warga, R.M., Allende, M.L., Weinberg, E.S., Nüsslein-Volhard, C. Development (1996) [Pubmed]
  6. Specification of cell fates at the dorsal margin of the zebrafish gastrula. Melby, A.E., Warga, R.M., Kimmel, C.B. Development (1996) [Pubmed]
  7. Mutant rescue by BAC clone injection in zebrafish. Yan, Y.L., Talbot, W.S., Egan, E.S., Postlethwait, J.H. Genomics (1998) [Pubmed]
  8. Ash1a and Neurogenin1 function downstream of Floating head to regulate epiphysial neurogenesis. Cau, E., Wilson, S.W. Development (2003) [Pubmed]
  9. The zebrafish floating head mutant demonstrates podocytes play an important role in directing glomerular differentiation. Majumdar, A., Drummond, I.A. Dev. Biol. (2000) [Pubmed]
  10. Spatial regulation of floating head expression in the developing notochord. Melby, A.E., Kimelman, D., Kimmel, C.B. Dev. Dyn. (1997) [Pubmed]
  11. Vessel patterning in the embryo of the zebrafish: guidance by notochord. Fouquet, B., Weinstein, B.M., Serluca, F.C., Fishman, M.C. Dev. Biol. (1997) [Pubmed]
  12. Restricted expression of the zebrafish hsp90alpha gene in slow and fast muscle fiber lineages. Sass, J.B., Martin, C.C., Krone, P.H. Int. J. Dev. Biol. (1999) [Pubmed]
  13. Genetic analysis of tissue interactions required for otic placode induction in the zebrafish. Mendonsa, E.S., Riley, B.B. Dev. Biol. (1999) [Pubmed]
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