title: Sonic hedgehog in temporal control of somite formation.
abstract: Vertebrate embryo somite formation is temporally controlled by the cyclic expression of somitogenesis clock genes in the presomitic mesoderm (PSM). The somitogenesis clock is believed to be an intrinsic property of this tissue, operating independently of embryonic midline structures and the signaling molecules produced therein, namely Sonic hedgehog (Shh). This work revisits the notochord signaling contribution to temporal control of PSM segmentation by assessing the rate and number of somites formed and somitogenesis molecular clock gene expression oscillations upon notochord ablation. The absence of the notochord causes a delay in somite formation, accompanied by an increase in the period of molecular clock oscillations. Shh is the notochord-derived signal responsible for this effect, as these alterations are recapitulated by Shh signaling inhibitors and rescued by an external Shh supply. We have characterized chick smoothened expression pattern and have found that the PSM expresses both patched1 and smoothened Shh signal transducers. Upon notochord ablation, patched1, gli1, and fgf8 are down-regulated, whereas gli2 and gli3 are overexpressed. Strikingly, notochord-deprived PSM segmentation rate recovers over time, concomitant with raldh2 overexpression. Accordingly, exogenous RA supplement rescues notochord ablation effects on somite formation. A model is presented in which Shh and RA pathways converge to inhibit PSM Gli activity, ensuring timely somite formation. Altogether, our data provide evidence that a balance between different pathways ensures the robustness of timely somite formation and that notochord-derived Shh is a component of the molecular network regulating the pace of the somitogenesis clock.
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.
authors.forename: Tatiana P
authors.initials: TP
authors.lastname: Resende
authors.forename: Mónica
authors.initials: M
authors.lastname: Ferreira
authors.forename: Marie-Aimée
authors.initials: MA
authors.lastname: Teillet
authors.forename: Ana Teresa
authors.initials: AT
authors.lastname: Tavares
authors.forename: Raquel P
authors.initials: RP
authors.lastname: Andrade
authors.forename: Isabel
authors.initials: I
authors.lastname: Palmeirim
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000235:genetics; D019521:Body Patterning / Q000187:drug effects; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009672:Notochord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019170:Somites / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D053823:Hedgehog Proteins; D014212:Tretinoin