title: no tail integrates two modes of mesoderm induction.
abstract: During early zebrafish development the nodal signalling pathway patterns the embryo into three germ layers, in part by inducing the expression of no tail (ntl), which is essential for correct mesoderm formation. When nodal signalling is inhibited ntl fails to be expressed in the dorsal margin, but ventral ntl expression is unaffected. These observations indicate that ntl transcription is under both nodal-dependent and nodal-independent regulation. Consistent with these observations and with a role for ntl in mesoderm formation, some somites form within the tail region of embryos lacking nodal signalling. In an effort to understand how ntl is regulated and thus how mesoderm forms, we have mapped the elements responsible for nodal-dependent and nodal-independent expression of ntl in the margin of the embryo. Our work demonstrates that expression of ntl in the margin is the consequence of two separate enhancers, which act to mediate different mechanisms of mesoderm formation. One of these enhancers responds to nodal signalling, and the other to Wnt and BMP signalling. We demonstrate that the nodal-independent regulation of ntl is essential for tail formation. Misexpression of Wnt and BMP ligands can induce the formation of an ectopic tail, which contains somites, in embryos devoid of nodal signalling, and this tail formation is dependent on ntl function. Similarly, nodal-independent tail somite formation requires ntl. At later stages in development ntl is required for notochord formation, and our analysis has also led to the identification of the enhancer required for ntl expression in the developing notochord.
authors.affiliation: Wellcome Trust and Cancer Research UK, Gurdon Institute and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. sh19@sanger.ac.uk
authors.forename: Steven A
authors.initials: SA
authors.lastname: Harvey
authors.forename: Stefan
authors.initials: S
authors.lastname: Tümpel
authors.forename: Julien
authors.initials: J
authors.lastname: Dubrulle
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
authors.forename: James C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000502:physiology*; D004627:Embryonic Induction / Q000502:physiology*; D005326:Fetal Proteins; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000502:physiology*; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction / Q000502:physiology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D055457:Nodal Protein; D020825:T-Box Domain Proteins; D029961:Zebrafish Proteins; D000098908:Brachyury Protein