Bessodes N , Haillot E , Duboc V , Röttinger E , Lahaye F , Lepage T .

	Figure 1. Establishment of left-right asymmetry in echinoderms.Left-right asymmetry in echinoderms is characterized by the asymmetric positioning of the imaginal rudiment on the left side of the bilateral pluteus larva. The adult emerges from this imaginal rudiment through metamorphosis. Formation of the rudiment is intimately linked to development of two mesodermal derivatives, the coelomic pouches, that form from an unpaired coelomic sac that budds off from the tip of the archenteron. The coelomic pouches are bilateral structures, but only the coelomic pouch located on the left side of the larva proliferates and differentiates to form the rudiment. Precursors of the coelomic pouches have a double origin. Part of these precursors derives from the small micromeres that form by asymmetric division of the large micromeres at 5th cleavage. These cells are thought to contribute to the germ line. Another population of coelomic pouch precursors derives from the non-skeletogenic mesoderm that is induced during blastula stages by Delta signals emanating from the skeletogenic mesenchymal cell precursors.
	Figure 2. Left-right asymmetric expression of nodal is initiated in a discrete endodermal territory.A, Whole-mount in situ hybridizations with a nodal probe. Asymmetric expression of nodal is first detected in the endoderm, several hours before the onset of asymmetric nodal expression in the ectoderm. AV, view from the animal pole; DV, view from the dorsal side; L, left; R, right. The black arrowheads highlight the beginning of nodal expression on the right side of the tip of the archenteron and in the ectoderm. The inset shows a high magnification view of the nodal expressing cells arranged in a rosette. B, Double fluorescent in situ hybridization with nodal (red) and either the endodermal marker gene foxA or the coelomic pouch marker gene foxF (green). The early expression of nodal is initiated in the endoderm territory underlying the coelomic pouch precursors that express foxF. The schemes on the right depict the territories expressing nodal (red) with respect to the mesodermal territory that expresses foxF and the endodermal territory that expresses foxA (green).
	Figure 3. Both inhibition of Notch signaling and inhibition of the H+/K+-ATPase cause bilateral expression of nodal in the endomesoderm and randomize nodal expression in the ectoderm.A, nodal expression in control embryos and in embryos treated with DAPT or omeprazole starting after fertilization or injected with a morpholino oligonucleotide against Delta. Black arrowheads show an ectopic expression of nodal on the left side. The percentages indicate the proportion of embryos showing the same sidedness of nodal expression as that showed in the panel. B, At pluteus stage, nodal and univin expression in DAPT-treated embryos or in Delta-morpholino injected embryos is randomized. C, The expression of pitx2, sox9 and foxF in the coelomic pouch precursors as well as the expression of tropomyosin in the muscle cell precursors is strongly reduced or absent in DAPT-treated embryos. D, Time course of DAPT treatments. Embryos were treated with DAPT starting at different stages and nodal expression was scored at pluteus stages. DAPT treatments perturb left-right asymmetry only when performed before hatching. VEB, very early blastula; EB, early blastula; SB, swimming blastula; MB, mesenchyme blastula. E, The window during which DAPT treatments interfere with left-right asymmetry coincides with the period during which non skeletogenic mesoderm precursors are induced by Delta/Notch signaling. AV, Animal views; DV, Dorsal views; L, Left; R, Right.
	Figure 4. Treatments with the H+/K+ATPase inhibitor omeprazole phenocopy inhibition of Notch signaling.A, Phenotype of control embryos and of embryos treated as indicated at late gastrula and at pluteus stages. DAPT, omeprazole-treated embryos and Delta morpholino injected embryos develop with a smooth archenteron that lacks delaminating secondary mesenchymal cells at late gastrula stage and that are albinos at pluteus stage. The black arrowhead shows pigment cells embedded in the ectoderm of control embryos. B, Whole mount in situ hybridization with mesodermal or endodermal molecular markers. The expression of the Delta target genes gcm, papss, and gata1/2/3 in the non-skeletogenic mesoderm territory is abolished in DAPT-treated and in omeprazole-treated embryos. In contrast, Delta, msp130 and foxA are expressed at normal levels in the skeletogenic primary mesenchymal cell precursors or endodermal precursors in DAPT-treated, omeprazole-treated or Delta morpholino injected embryos. Vegetal pole views of control and treated embryos are shown in the upper corners. Note, that the expression of foxA in the Delta Morpholino injected embryos and in the DAPT or omeprazole treated embryos, has expanded towards the vegetal pole, consistent with the absence of mesodermal precursors in these embryos. SB, swimming blastula; MB, mesenchyme blastula. Embryos are in frontal views. C, Luciferase assays with the Notch reporter RBP-JK. Omeprazole strongly inhibits Notch signaling induced by overexpression of Delta but has no effect on Notch signaling induced by overexpression of NEXT or NICD.
	Figure 5. FGF/MAP kinase signaling is required for nodal expression in the left-right organizer.A, The early asymmetrical expression of nodal in the endoderm is lost following inhibition of FGFR/MAPK signaling. In embryos treated with the FGF receptor inhibitor SU5402 or the MEK inhibitor U0126 from fertilization onwards, nodal expression is not initiated in the endomesoderm. DAPT treated embryos show bilateral expression of nodal in the endomesoderm but embryos treated with DAPT followed by U0126 treatment at mesenchyme blastula stage do not express nodal in the endomesoderm. B, Inhibition of ERK or FGF signaling randomizes nodal and univin expression in the ectoderm as well as pitx2 and sox9 expression in the coelomic pouch precursors at pluteus stage. C, Inhibition of MAPK signaling randomizes the positioning of the rudiment. D, Time course of U0126 treatments. Embryos were treated with U0126 starting at the indicated stages and the sidedness of nodal expression was scored at pluteus stage. The efficiency of U0126 treatment on left-right asymmetry drops after 22 hpf, which coincides with the onset of asymmetrical expression of nodal in the endoderm. The percentages and total number of embryos in each experiment are indicated at the bottom of pictures. E, The drop in the ability of U0126 to block nodal expression coincides with the onset of asymmetrical expression of nodal in the endoderm. AV, animal views; DV, dorsal views; L, left; R, right.
	Figure 6. BMP signaling is required for nodal expression in the left-right organizer.A, nodal expression in the endomesoderm requires BMP signaling. Both treatments with BMP4 protein and injection of bmp2/4 or alk3/6 morpholinos abolish nodal expression in the endoderm at gastrula stage. B, nodal expression at pluteus stage in the bmp2/4 or alk3/6 morphants. Following inhibition of bmp2/4 or alk3/6 by morpholino injection into the egg, nodal expression occurs randomly on the left or right sides. The arrowheads point to the expansion of nodal to the dorsal part of the ciliary band. C,D, Alk3/6 function is required in the endomesoderm for nodal expression in the left-right organizer. Following injection of alk3/6 morpholino into the four vegetal blastomeres, nodal expression is not inititated in the endomesoderm and is randomized at pluteus stage. E–G, Effects of inhibiting BMP signaling on either the left or the right side on nodal expression. Embryos were injected with the bmp2/4 morpholino together with FLDX (green) into one blastomere at the two-cell stage, the position of the lineage tracer was revealed after in situ hybridization (red in pictures). F Injection of the bmp2/4 morpholino targeting the left side more strongly affected nodal expression in the organizer at gastrula stage than injections targeted to the right side. Injection of the bmp2/4 morpholino on the left but not on the right side randomizes nodal expression at pluteus stage. H, BMP signaling in the endomesoderm is biased towards the left side at late gastrula stage. Fluorescence microscope images (3 middle images) and confocal microscope image (lower picture) of embryos at the late gastrula stage immunostained with an anti phospho Smad1/5/8 reveal a domain of strong BMP signaling near the tip of the archenteron. This staining was asymmetric in about two third of the embryos, with stronger staining in the dorsal-left sector of the archenteron opposite to the nodal expressing territory. AV, animal view; DV, dorsal view; plut, pluteus larva; R, right side; L, left side.
	Figure 7. Establishment of left-right asymmetry requires reciprocal Nodal signaling between the ectoderm and endomesoderm.A,B ectodermal Nodal signals are required for nodal expression in the endomesoderm. A, Experimental design. The four animal blastomeres of a 8-cell stage embryo were injected with a nodal morpholino and nodal expression was analyzed at the gastrula stage. B, DIC and Fluorescent images of injected larvae and whole mount in situ hybridization of injected embryos with the nodal probe. Blocking nodal mRNA translation in the ectoderm abolishes nodal expression in the endomesoderm at gastrula stage and radializes the embryos. C,D, nodal signaling in the endomesoderm is required for establishment of left-right asymmetry in the ectoderm. C, Experimental design. The vegetal half (four blastomeres) of embryos at the eight-cell stage were injected with the alk4/5/7 morpholino. D, DIC and Fluorescent images of injected larvae and whole mount in situ hybridization of embryos with the nodal probe. nodal is expressed on the right side of the ectoderm in control embryos but in 9 out of 19 injected embryos, nodal expression is detected on the left side. pitx2 is expressed on the right side of the endomesoderm in control embryos but in 5 out of 6 alk4/5/7 morpholino injected embryos, pitx2 expression is lost. E,F, Mosaic analysis using chimeric embryos produced by microsurgery. E, Experimental design. The vegetal half of a nodal morphant (green) was combined with a control animal half (grey). F, Fluorescent and DIC images of a chimeric larvae and whole mount in situ hybridization of chimeric embryos with a nodal probe. nodal is expressed on the right side of the ectoderm in control embryos but in 5 out of 12 chimeric embryos, nodal expression is detected on the left side. V, ventral; D, dorsal; LV, lateral view; AV, animal pole view; L, left; R, right; An, animal pole; Veg, vegetal pole.
	Figure 8. Long-range Nodal signaling within the ectoderm and between the ectoderm and the endodermal left-right organizer requires Univin.A, Experimental design to test the role of Univin in long-range signaling of Nodal during establishment of left-right asymmetry. Following injection of the nodal morpholino into the egg, a synthetic nodal mRNA (immune against the morpholino) alone or a mixture of nodal+univin mRNAs were injected into one animal blastomere (presumptive ectoderm) of embryos at the 8-cell stage B, Experimental results. Injection of the nodal morpholino alone abolishes pitx2 expression and causes bilateral expression of sox9. In this nodal morpholino background, local injection of nodal mRNA alone into one blastomere at the 8-cell stage does not rescue pitx2 expression but co-injection of nodal and univin mRNAs efficiently induces pitx2 at a long distance from the injection clone. The fluorescent images show a Nodal morpholino injected larva (RLDX fluorescence) or larvae rescued by injection of nodal mRNA or by a combination of both nodal and univin mRNAs into one blastomere at the 8-cell stage (merged images of RLDX and FLDX fluorescence).
	Figure 9. Model for establishment of left-right asymmetry by reciprocal signaling between the ectoderm and the endomesoderm.A, At midgastrula stage, nodal is expressed asymmetrically in endodermal cells on the right side under the influence of both positive (FGF and BMP signaling) and negative (signal X) inputs. At this stage, nodal is also expressed symmetrically in the ventral ectoderm. In contrast, univin is expressed more laterally in the presumptive ciliary band ectoderm and throughout the endoderm. As a consequence, the nodal and univin territories only partially overlap in the archenteron and in two ectodermal regions flanking the presumptive stomodeum (purple color). At this stage, while expression of nodal in the ventral ectoderm vanishes, asymmetrical Nodal+Univin signaling on the right side of the archenteron induces nodal expression in the lateral right ectoderm that expresses univin creating a novel Nodal+Univin expressing signaling center on the right side. The reaction-diffusion mechanism between Nodal and Lefty stabilizes nodal expression on the right side and prevents its expansion to the rest of the embryo. B, Summary diagrams of the experiments. Both the loss of nodal expression in the endoderm caused by inhibition of the FGF or BMP pathways or the bilateralisation of nodal expression in the endoderm caused by inhibition of Notch signaling, randomize nodal expression in the ectoderm at pluteus stage. In the endoderm, FGF/ERK positively regulates nodal expression on the right side while unidentified signals coming from the mesoderm induced by Delta/Notch signaling negatively regulate nodal expression on the left side of the archenteron. The window during which SU5402 and UO126 are effective at perturbing left-right asymmetry extends from fertilization to mesenchyme blastula/gastrula stage (green shading). H+/K+-ATPase acts on Delta/Notch signaling to regulate left-right asymmetry. The window during which DAPT (red shading) and omeprazole (blue shading) are effective on left-right asymmetry extends from egg up to the early blastula stage. Inhibition of Nodal or BMP signaling in the endomesoderm randomizes nodal expression in ectoderm. Injection of nodal mRNA alone fails to rescue left-right asymmetry and pitx2 expression in embryos previously injected with a nodal morpholino but coinjection of nodal+univin mRNAs efficiently rescues pitx2 expression in the coelomic pouch and ciliary band. In most of these embryos, pitx2 is expressed more strongly on the right side. An, animal pole; Veg, vegetal pole.
	Figure 10. Multiple signals cooperate to establish a left-right endodermal organizer in the sea urchin embryo.Biotapestry diagram describing the gene regulatory interactions identified in this study that specify the left-right endodermal organizer. During gastrulation, Nodal and Univin signals produced by the ventral ectoderm induce nodal and univin expression on the right side of the endoderm territory while non-skeletogenic mesodermal cells specified by Delta/Notch signaling send a putative inhibitory signal (signal X) that represses nodal expression on the left side of the adjacent endodermal territory. At gastrula stage, BMP signals emanating from the ventral ectoderm that expresses bmp2/4 are received on the dorsal sector of the archenteron where they induce an unknown signal (signal Y) that cooperates with FGF signaling to induce nodal expression on the ventral-right side of the endoderm territory. Cell interactions between the left-right organizer located in the ventral-right sector and the dorsal endoderm further pattern this region causing BMP signaling to be restricted to the left portion of archenteron. Note that production of signal X may involve several steps and that the origin of the FGF signal is not known. Nodal and Univin signals emanating from the ventral-right endodermal region in turn promote nodal, univin and pitx2 expression on the right side of the ciliary band ectoderm and prevent rudiment formation on the right side in part by repressing the expression of genes encoding germ line specific factors such as Sox9 [10].
	Figure 11. Comparison between vertebrates and echinoderms: the laterality information emanating from a mesendodermal left-right organizer propagates to distant tissues through Nodal/Univin signaling.In vertebrates, the asymmetric expression of nodal is initiated in a discrete region on the midline that plays the role of a left-right organizer (the node in mammals, the Küpffer vesicle in zebrafish or the gastrocoel roof in amphibians). H+/K+-ATPases, Delta/Notch and FGF signaling as well as cilia driven leftward flow have been implicated in the symmetry breaking process. Nodal expression subsequently propagates to the lateral regions of the embryos by mechanisms that involve long-range signaling by Nodal and GDF1 as well as communication with endodermal cells through gap junctions. In the sea urchin embryo, H+/K+-ATPase, Delta/Notch and FGF signaling are involved in the initiation of asymmetrical expression of nodal in a discrete region of the archenteron that appears to play the role of a left-right organizer. In the sea urchin, the laterality information is relayed from the left-right organizer to more distant regions through long range Nodal-Univin signaling.

Aihara, Inversion of left-right asymmetry in the formation of the adult rudiment in sea urchin larvae: removal of a part of embryos at the gastrula stage. 2000, Pubmed, Echinobase

Aihara, Inversion of left-right asymmetry in the formation of the adult rudiment in sea urchin larvae: removal of a part of embryos at the gastrula stage. 2000, Pubmed , Echinobase
Anstrom, Localization and expression of msp130, a primary mesenchyme lineage-specific cell surface protein in the sea urchin embryo. 1987, Pubmed , Echinobase
Arnone, Using reporter genes to study cis-regulatory elements. 2004, Pubmed , Echinobase
Blum, Evolution of leftward flow. 2009, Pubmed
Boorman, The evolution of left-right asymmetry in chordates. 2002, Pubmed
Brennan, Nodal activity in the node governs left-right asymmetry. 2002, Pubmed
Burdine, Conserved and divergent mechanisms in left-right axis formation. 2000, Pubmed
Burke, A genomic view of the sea urchin nervous system. 2006, Pubmed , Echinobase
Burn, Left-right asymmetry in gut development: what happens next? 2009, Pubmed
Campione, The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping. 1999, Pubmed
Caron, Wnt/β-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer's vesicle. 2012, Pubmed
Chang, Smad5 is essential for left-right asymmetry in mice. 2000, Pubmed
Cheng, Lefty blocks a subset of TGFbeta signals by antagonizing EGF-CFC coreceptors. 2004, Pubmed
Chocron, Zebrafish Bmp4 regulates left-right asymmetry at two distinct developmental time points. 2007, Pubmed
Coutelis, Left-right asymmetry in Drosophila. 2008, Pubmed
Croce, Dynamics of Delta/Notch signaling on endomesoderm segregation in the sea urchin embryo. 2010, Pubmed , Echinobase
Croce, Frizzled5/8 is required in secondary mesenchyme cells to initiate archenteron invagination during sea urchin development. 2006, Pubmed , Echinobase
Duboc, Left-right asymmetry in the sea urchin embryo is regulated by nodal signaling on the right side. 2005, Pubmed , Echinobase
Duboc, A conserved role for the nodal signaling pathway in the establishment of dorso-ventral and left-right axes in deuterostomes. 2008, Pubmed , Echinobase
Duboc, Nodal and BMP2/4 pattern the mesoderm and endoderm during development of the sea urchin embryo. 2010, Pubmed , Echinobase
Duboc, Nodal and BMP2/4 signaling organizes the oral-aboral axis of the sea urchin embryo. 2004, Pubmed , Echinobase
Duboc, Lefty acts as an essential modulator of Nodal activity during sea urchin oral-aboral axis formation. 2008, Pubmed , Echinobase
Emily-Fenouil, GSK3beta/shaggy mediates patterning along the animal-vegetal axis of the sea urchin embryo. 1998, Pubmed , Echinobase
Essner, Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut. 2005, Pubmed
Ettensohn, Cell interactions and mesodermal cell fates in the sea urchin embryo. 1992, Pubmed , Echinobase
Fujiwara, Distinct requirements for extra-embryonic and embryonic bone morphogenetic protein 4 in the formation of the node and primitive streak and coordination of left-right asymmetry in the mouse. 2002, Pubmed
Furtado, BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4. 2008, Pubmed
Gottardi, An ion-transporting ATPase encodes multiple apical localization signals. 1993, Pubmed
Gourronc, Nodal activity around Kupffer's vesicle depends on the T-box transcription factors Notail and Spadetail and on Notch signaling. 2007, Pubmed
Grande, Nodal signalling is involved in left-right asymmetry in snails. 2009, Pubmed , Echinobase
Gros, Cell movements at Hensen's node establish left/right asymmetric gene expression in the chick. 2009, Pubmed
Harland, In situ hybridization: an improved whole-mount method for Xenopus embryos. 1991, Pubmed
Hibino, Ion flow regulates left-right asymmetry in sea urchin development. 2006, Pubmed , Echinobase
Hirokawa, Nodal flow and the generation of left-right asymmetry. 2006, Pubmed
Hyatt, Initiation of vertebrate left-right axis formation by maternal Vg1. 1996, Pubmed
Kawakami, Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo. 2005, Pubmed
Kishigami, BMP signaling through ACVRI is required for left-right patterning in the early mouse embryo. 2004, Pubmed
Kitazawa, Micromere-derived signal regulates larval left-right polarity during sea urchin development. 2007, Pubmed , Echinobase
Kramer, Ectodermal syndecan-2 mediates left-right axis formation in migrating mesoderm as a cell-nonautonomous Vg1 cofactor. 2002, Pubmed
Kramer-Zucker, Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis. 2005, Pubmed
Krebs, Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. 2003, Pubmed
Lapraz, Patterning of the dorsal-ventral axis in echinoderms: insights into the evolution of the BMP-chordin signaling network. 2009, Pubmed , Echinobase
Lepage, Purification and characterization of the sea urchin embryo hatching enzyme. 1989, Pubmed , Echinobase
Levin, Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning. 2002, Pubmed
Levin, Left-right asymmetry in vertebrate embryogenesis. 1997, Pubmed
Levin, Gap junction-mediated transfer of left-right patterning signals in the early chick blastoderm is upstream of Shh asymmetry in the node. 1999, Pubmed
Levin, Left-right asymmetry in embryonic development: a comprehensive review. 2005, Pubmed
Logan, Nuclear beta-catenin is required to specify vegetal cell fates in the sea urchin embryo. 1999, Pubmed , Echinobase
Longabaugh, Visualization, documentation, analysis, and communication of large-scale gene regulatory networks. 2009, Pubmed
Lopes, Notch signalling regulates left-right asymmetry through ciliary length control. 2010, Pubmed
Lu, Function of Rieger syndrome gene in left-right asymmetry and craniofacial development. 1999, Pubmed
Materna, A comprehensive analysis of Delta signaling in pre-gastrular sea urchin embryos. 2012, Pubmed , Echinobase
McClay, A micromere induction signal is activated by beta-catenin and acts through notch to initiate specification of secondary mesenchyme cells in the sea urchin embryo. 2000, Pubmed , Echinobase
McGrath, Cilia are at the heart of vertebrate left-right asymmetry. 2003, Pubmed
Meno, Left-right asymmetric expression of the TGF beta-family member lefty in mouse embryos. 1996, Pubmed
Meno, lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal. 1998, Pubmed
Mercola, Left-right asymmetry: nodal points. 2003, Pubmed
Minoguchi, RBP-L, a transcription factor related to RBP-Jkappa. 1997, Pubmed
Monsoro-Burq, Left-right asymmetry in BMP4 signalling pathway during chick gastrulation. 2000, Pubmed
Nakamura, Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system. 2006, Pubmed
Neugebauer, FGF signalling during embryo development regulates cilia length in diverse epithelia. 2009, Pubmed
Nonaka, Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. 1998, Pubmed
Okada, Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination. 2005, Pubmed
Okumura, The development and evolution of left-right asymmetry in invertebrates: lessons from Drosophila and snails. 2008, Pubmed
Oliveri, Repression of mesodermal fate by foxa, a key endoderm regulator of the sea urchin embryo. 2006, Pubmed , Echinobase
Patlolla, Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats. 2012, Pubmed
Pehrson, The fate of the small micromeres in sea urchin development. 1986, Pubmed , Echinobase
Peter, The endoderm gene regulatory network in sea urchin embryos up to mid-blastula stage. 2010, Pubmed , Echinobase
Piedra, BMP signaling positively regulates Nodal expression during left right specification in the chick embryo. 2002, Pubmed
Przemeck, Node and midline defects are associated with left-right development in Delta1 mutant embryos. 2003, Pubmed
Ramsdell, Molecular mechanisms of vertebrate left-right development. 1998, Pubmed
Rand, Calcium depletion dissociates and activates heterodimeric notch receptors. 2000, Pubmed
Range, Cis-regulatory analysis of nodal and maternal control of dorsal-ventral axis formation by Univin, a TGF-beta related to Vg1. 2007, Pubmed , Echinobase
Rankin, Regulation of left-right patterning in mice by growth/differentiation factor-1. 2000, Pubmed
Ransick, cis-regulatory processing of Notch signaling input to the sea urchin glial cells missing gene during mesoderm specification. 2006, Pubmed , Echinobase
Raya, Left-right asymmetry in the vertebrate embryo: from early information to higher-level integration. 2006, Pubmed
Raya, Notch activity induces Nodal expression and mediates the establishment of left-right asymmetry in vertebrate embryos. 2003, Pubmed
Raya, Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination. 2004, Pubmed
Roy, The multifaceted role of Notch in cancer. 2007, Pubmed
Ruffins, A fate map of the vegetal plate of the sea urchin (Lytechinus variegatus) mesenchyme blastula. 1996, Pubmed , Echinobase
Röttinger, FGF signals guide migration of mesenchymal cells, control skeletal morphogenesis [corrected] and regulate gastrulation during sea urchin development. 2008, Pubmed , Echinobase
Röttinger, Nemo-like kinase (NLK) acts downstream of Notch/Delta signalling to downregulate TCF during mesoderm induction in the sea urchin embryo. 2006, Pubmed , Echinobase
Saijoh, Left-right patterning of the mouse lateral plate requires nodal produced in the node. 2003, Pubmed
Saudemont, Ancestral regulatory circuits governing ectoderm patterning downstream of Nodal and BMP2/4 revealed by gene regulatory network analysis in an echinoderm. 2010, Pubmed , Echinobase
Schlange, BMP2 is a positive regulator of Nodal signaling during left-right axis formation in the chicken embryo. 2002, Pubmed
Schweickert, Cilia-driven leftward flow determines laterality in Xenopus. 2007, Pubmed
Schweickert, Linking early determinants and cilia-driven leftward flow in left-right axis specification of Xenopus laevis: a theoretical approach. 2012, Pubmed
Schweisguth, Regulation of notch signaling activity. 2004, Pubmed
Sethi, Sequential signaling crosstalk regulates endomesoderm segregation in sea urchin embryos. 2012, Pubmed , Echinobase
Sherwood, LvNotch signaling mediates secondary mesenchyme specification in the sea urchin embryo. 1999, Pubmed , Echinobase
Smith, Bmp and nodal independently regulate lefty1 expression to maintain unilateral nodal activity during left-right axis specification in zebrafish. 2011, Pubmed
Sutherland, Disorders of left-right asymmetry: heterotaxy and situs inversus. 2009, Pubmed
Sweet, The role of micromere signaling in Notch activation and mesoderm specification during sea urchin embryogenesis. 1999, Pubmed , Echinobase
Sweet, LvDelta is a mesoderm-inducing signal in the sea urchin embryo and can endow blastomeres with organizer-like properties. 2002, Pubmed , Echinobase
Tabin, Do we know anything about how left-right asymmetry is first established in the vertebrate embryo? 2005, Pubmed
Takata, Pigment cells trigger the onset of gastrulation in tropical sea urchin Echinometra mathaei. 2004, Pubmed , Echinobase
Tanaka, FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. 2005, Pubmed
Tanaka, Long-range action of Nodal requires interaction with GDF1. 2007, Pubmed
Tsiairis, An Hh-dependent pathway in lateral plate mesoderm enables the generation of left/right asymmetry. 2009, Pubmed
Udelnow, Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. 2011, Pubmed
Vaccari, The vacuolar ATPase is required for physiological as well as pathological activation of the Notch receptor. 2010, Pubmed
Vandenberg, Far from solved: a perspective on what we know about early mechanisms of left-right asymmetry. 2010, Pubmed
Viotti, Role of the gut endoderm in relaying left-right patterning in mice. 2012, Pubmed
Walentek, ATP4a is required for Wnt-dependent Foxj1 expression and leftward flow in Xenopus left-right development. 2012, Pubmed
Yaguchi, Specification of ectoderm restricts the size of the animal plate and patterns neurogenesis in sea urchin embryos. 2006, Pubmed , Echinobase
Yan, The vacuolar proton pump, V-ATPase, is required for notch signaling and endosomal trafficking in Drosophila. 2009, Pubmed
Yasui, Left-right asymmetric expression of BbPtx, a Ptx-related gene, in a lancelet species and the developmental left-sidedness in deuterostomes. 2000, Pubmed
Yoshioka, Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry. 1998, Pubmed
de-Leon, Information processing at the foxa node of the sea urchin endomesoderm specification network. 2010, Pubmed , Echinobase