title: Retinoic acid regulation of the Mesp-Ripply feedback loop during vertebrate segmental patterning.
abstract: The Mesp bHLH genes play a conserved role during segmental patterning of the mesoderm in the vertebrate embryo by specifying segmental boundaries and anteroposterior (A-P) segmental polarity. Here we use a xenotransgenic approach to compare the transcriptional enhancers that drive expression of the Mesp genes within segments of the presomitic mesoderm (PSM) of different vertebrate species. We find that the genomic sequences upstream of the mespb gene in the pufferfish Takifugu rubripes (Tr-mespb) are able to drive segmental expression in transgenic Xenopus embryos while those from the Xenopus laevis mespb (Xl-mespb) gene drive segmental expression in transgenic zebrafish. In both cases, the anterior segmental boundary of transgene expression closely matches the expression of the endogenous Mesp genes, indicating that many inputs into segmental gene expression are highly conserved. By contrast, we find that direct retinoic acid (RA) regulation of endogenous Mesp gene expression is variable among vertebrate species. Both Tr-mespb and Xl-mespb are directly upregulated by RA, through a complex, distal element. By contrast, RA represses the zebrafish Mesp genes. We show that this repression is mediated, in part, by RA-mediated activation of the Ripply genes, which together with Mesp genes form an RA-responsive negative feedback loop. These observations suggest that variations in a direct response to RA input may allow for changes in A-P patterning of the segments in different vertebrate species.
authors.affiliation: The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Tanya A
authors.initials: TA
authors.lastname: Moreno
authors.forename: Roberto
authors.initials: R
authors.lastname: Jappelli
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisúa Belmonte
authors.forename: Chris
authors.initials: C
authors.lastname: Kintner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D005075:Biological Evolution; D019521:Body Patterning / Q000187:drug effects* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005246:Feedback; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008954:Models, Biological; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012097:Repressor Proteins / Q000235:genetics*; D019170:Somites / Q000196:embryology; D013045:Species Specificity; D023741:Takifugu / Q000196:embryology / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014714:Vertebrates / Q000196:embryology* / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D012097:Repressor Proteins; D014212:Tretinoin; D029867:Xenopus Proteins; C530218:Mespb protein, Xenopus