Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Dev Biol
2008 Mar 15;3152:317-30. doi: 10.1016/j.ydbio.2007.12.038.
Show Gene links
Show Anatomy links
Retinoic acid regulation of the Mesp-Ripply feedback loop during vertebrate segmental patterning.
Moreno TA
,
Jappelli R
,
Izpisúa Belmonte JC
,
Kintner C
.
???displayArticle.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.
Fig. 1. Mesp genes in Xenopus. (A) Genomic organization of the Mesp genes. Shown are syntenic genomic regions from mouse, Xenopus tropicalis, Takifugu rubripes and Danio rerio. Chromosome number is given when available, otherwise, scaffold number is indicated. Boxing indicates synteny of genes. X. tropicalis genes ENSXETG00000017725 and ENSXETG00000027628 are designated as mespb and mespa respectively. Green triangles indicate a syntenic block of 6 genes that are conserved between X. tropicalis and mouse, but in frog this block is between mespa and the AnPep gene, while in mouse the block is located 4 megabases (mb) away. (B, C) Expression of Xl-mespa and Xl-mespb in the PSM of X. laevis embryos by whole mount in situ hybridization. Dotted lines indicate approximate locations of somitomere boundaries. (D) Double in situ hybridization with Xl-mespb (red) and Xl-mespa (purple). (E–L) Shown is the expression of Xenopus Mesp genes after treatment with CHX and RA, as indicated. Treatment was for 1.5 h at RT prior to fixation. (M) Schematic representation of the PSM showing the relative locations of the somitomeres, transition zone (TZ) and tailbud (TBD) with X. laevis Mesp expression patterns indicated. Anterior is to the left in all panels.
Xenopus mespa gene expression in paraxial mesoderm
Aparicio,
Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes.
2002, Pubmed
Aparicio,
Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes.
2002,
Pubmed
Aulehla,
Segmentation in vertebrates: clock and gradient finally joined.
2004,
Pubmed
Brand-Saberi,
Evolution and development of distinct cell lineages derived from somites.
2000,
Pubmed
Brenner,
Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome.
1993,
Pubmed
Buchberger,
Dynamic expression of chicken cMeso2 in segmental plate and somites.
2002,
Pubmed
Buchberger,
cMeso-1, a novel bHLH transcription factor, is involved in somite formation in chicken embryos.
1998,
Pubmed
Chan,
Ledgerline, a novel Xenopus laevis gene, regulates differentiation of presomitic mesoderm during somitogenesis.
2006,
Pubmed
,
Xenbase
Christ,
The development of the avian vertebral column.
2000,
Pubmed
Christen,
FGF-8 is associated with anteroposterior patterning and limb regeneration in Xenopus.
1997,
Pubmed
,
Xenbase
Cooke,
A clock and wavefront model for control of the number of repeated structures during animal morphogenesis.
1976,
Pubmed
,
Xenbase
Davis,
Molecular targets of vertebrate segmentation: two mechanisms control segmental expression of Xenopus hairy2 during somite formation.
2001,
Pubmed
,
Xenbase
Diez del Corral,
Opposing FGF and retinoid pathways control ventral neural pattern, neuronal differentiation, and segmentation during body axis extension.
2003,
Pubmed
Dubrulle,
From head to tail: links between the segmentation clock and antero-posterior patterning of the embryo.
2002,
Pubmed
Dubrulle,
fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo.
2004,
Pubmed
Dubrulle,
FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation.
2001,
Pubmed
Gridley,
The long and short of it: somite formation in mice.
2006,
Pubmed
Harland,
In situ hybridization: an improved whole-mount method for Xenopus embryos.
1991,
Pubmed
,
Xenbase
Hollemann,
Regionalized metabolic activity establishes boundaries of retinoic acid signalling.
1998,
Pubmed
,
Xenbase
Hollway,
Whole-somite rotation generates muscle progenitor cell compartments in the developing zebrafish embryo.
2007,
Pubmed
Hrabĕ de Angelis,
Maintenance of somite borders in mice requires the Delta homologue DII1.
1997,
Pubmed
Jen,
The Notch ligand, X-Delta-2, mediates segmentation of the paraxial mesoderm in Xenopus embryos.
1997,
Pubmed
,
Xenbase
Jen,
Periodic repression of Notch pathway genes governs the segmentation of Xenopus embryos.
1999,
Pubmed
,
Xenbase
Joseph,
Mespo: a novel basic helix-loop-helix gene expressed in the presomitic mesoderm and posterior tailbud of Xenopus embryos.
1999,
Pubmed
,
Xenbase
Kawakami,
Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo.
2005,
Pubmed
Kawamura,
Groucho-associated transcriptional repressor ripply1 is required for proper transition from the presomitic mesoderm to somites.
2005,
Pubmed
Keyse,
Protein phosphatases and the regulation of mitogen-activated protein kinase signalling.
2000,
Pubmed
Kim,
The protocadherin PAPC establishes segmental boundaries during somitogenesis in xenopus embryos.
2000,
Pubmed
,
Xenbase
Kondow,
Bowline, a novel protein localized to the presomitic mesoderm, interacts with Groucho/TLE in Xenopus.
2006,
Pubmed
,
Xenbase
Kroll,
Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation.
1996,
Pubmed
,
Xenbase
Kumar,
A molecular timescale for vertebrate evolution.
1998,
Pubmed
Li,
Cyclic expression of esr9 gene in Xenopus presomitic mesoderm.
2003,
Pubmed
,
Xenbase
Mason,
A novel MAP kinase phosphatase is localised in the branchial arch region and tail tip of Xenopus embryos and is inducible by retinoic acid.
1996,
Pubmed
,
Xenbase
Moreno,
Regulation of segmental patterning by retinoic acid signaling during Xenopus somitogenesis.
2004,
Pubmed
,
Xenbase
Morimoto,
The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite.
2007,
Pubmed
Morimoto,
Cooperative Mesp activity is required for normal somitogenesis along the anterior-posterior axis.
2006,
Pubmed
Morimoto,
The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity.
2005,
Pubmed
Nakajima,
Identification of Epha4 enhancer required for segmental expression and the regulation by Mesp2.
2006,
Pubmed
Nomura-Kitabayashi,
Hypomorphic Mesp allele distinguishes establishment of rostrocaudal polarity and segment border formation in somitogenesis.
2002,
Pubmed
Pourquie,
The vertebrate segmentation clock.
2001,
Pubmed
Rastinejad,
Retinoid X receptor and its partners in the nuclear receptor family.
2001,
Pubmed
Saga,
The making of the somite: molecular events in vertebrate segmentation.
2001,
Pubmed
Saga,
Genetic rescue of segmentation defect in MesP2-deficient mice by MesP1 gene replacement.
1998,
Pubmed
Saga,
Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation.
1997,
Pubmed
Saga,
MesP1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation.
1996,
Pubmed
Sawada,
Fgf/MAPK signalling is a crucial positional cue in somite boundary formation.
2001,
Pubmed
Sawada,
Zebrafish Mesp family genes, mesp-a and mesp-b are segmentally expressed in the presomitic mesoderm, and Mesp-b confers the anterior identity to the developing somites.
2000,
Pubmed
Sparrow,
A simplified method of generating transgenic Xenopus.
2000,
Pubmed
,
Xenbase
Sparrow,
Thylacine 1 is expressed segmentally within the paraxial mesoderm of the Xenopus embryo and interacts with the Notch pathway.
1998,
Pubmed
,
Xenbase
Takahashi,
Feedback loops comprising Dll1, Dll3 and Mesp2, and differential involvement of Psen1 are essential for rostrocaudal patterning of somites.
2003,
Pubmed
Takahashi,
Differential contributions of Mesp1 and Mesp2 to the epithelialization and rostro-caudal patterning of somites.
2005,
Pubmed
Takahashi,
Appropriate suppression of Notch signaling by Mesp factors is essential for stripe pattern formation leading to segment boundary formation.
2007,
Pubmed
Terasaki,
Transgenic analysis of the medaka mesp-b enhancer in somitogenesis.
2006,
Pubmed
,
Xenbase
Turner,
Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate.
1994,
Pubmed
,
Xenbase
Vermot,
Retinoic acid coordinates somitogenesis and left-right patterning in vertebrate embryos.
2005,
Pubmed
Vermot,
Retinoic acid controls the bilateral symmetry of somite formation in the mouse embryo.
2005,
Pubmed
