Gene Symbol: Lefty1
Description: left right determination factor 1
Alias: AI450052, Ebaf, Leftb, Stra3, Tgfb4, lefty, lefty-1, left-right determination factor 1, TGF-beta-4, left-right determination, factor B, protein lefty-1, stimulated by retinoic acid gene 3 protein, transforming growth factor beta-4
Species: mouse
Products:     Lefty1

Top Publications

  1. Norris D, Brennan J, Bikoff E, Robertson E. The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo. Development. 2002;129:3455-68 pubmed
    ..However loss of the ASE disrupts Lefty2 (Leftb) expression and causes delayed Pitx2 expression leading to late onset, relatively minor LR patterning defects...
  2. Brennan J, Norris D, Robertson E. Nodal activity in the node governs left-right asymmetry. Genes Dev. 2002;16:2339-44 pubmed
    ..Our findings confirm that the mouse node is instrumental in initiating left-right axis specification and identify Nodal as the key morphogen regulating this process. ..
  3. Maisonneuve C, Guilleret I, Vick P, Weber T, Andre P, Beyer T, et al. Bicaudal C, a novel regulator of Dvl signaling abutting RNA-processing bodies, controls cilia orientation and leftward flow. Development. 2009;136:3019-30 pubmed publisher
    ..These results suggest a model whereby BicC links the orientation of cilia with PCP, possibly by regulating RNA silencing in P-bodies. ..
  4. Lowe L, Yamada S, Kuehn M. Genetic dissection of nodal function in patterning the mouse embryo. Development. 2001;128:1831-43 pubmed
    ..We find that nodal signaling is required for correct positioning of the anteroposterior axis, normal anterior and midline patterning, and the left-right asymmetric development of the heart, vasculature, lungs and stomach. ..
  5. Mayer G, Hamelin J, Asselin M, Pasquato A, Marcinkiewicz E, Tang M, et al. The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates. J Biol Chem. 2008;283:2373-84 pubmed
    ..after stimulation, the protease activity of PC5A is enhanced, as evidenced by the cleavage of the PC5A substrates Lefty, ADAMTS-4, endothelial lipase, and PCSK9...
  6. Saijoh Y, Oki S, Ohishi S, Hamada H. Left-right patterning of the mouse lateral plate requires nodal produced in the node. Dev Biol. 2003;256:160-72 pubmed
    ..These results indicate that Nodal produced in the node is required for expression of Nodal and other left side-specific genes in the LPM. ..
  7. Beck S, Le Good J, Guzman M, Ben Haim N, Roy K, Beermann F, et al. Extraembryonic proteases regulate Nodal signalling during gastrulation. Nat Cell Biol. 2002;4:981-5 pubmed
    ..A lack of Spc1 and Spc4 affects both pathways because these proteases also stimulate induction of Bmp4. ..
  8. Andersson O, Bertolino P, Ibanez C. Distinct and cooperative roles of mammalian Vg1 homologs GDF1 and GDF3 during early embryonic development. Dev Biol. 2007;311:500-11 pubmed
  9. Larkins C, Long A, Caspary T. Defective Nodal and Cerl2 expression in the Arl13b(hnn) mutant node underlie its heterotaxia. Dev Biol. 2012;367:15-24 pubmed publisher
    ..Symmetric Nodal and Cerl2 in the node could result from defects in either the generation and/ or the detection of Nodal flow, which would account for the subsequent defects in the LPM and organ positioning. ..

More Information


  1. Meno C, Ito Y, Saijoh Y, Matsuda Y, Tashiro K, Kuhara S, et al. Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos. Genes Cells. 1997;2:513-24 pubmed
    ..TGFbeta-related genes such as lefty and nodal are L-R asymmetrically expressed in developing mouse embryos, and may be involved in L-R determination...
  2. Chen C, Shen M. Two modes by which Lefty proteins inhibit nodal signaling. Curr Biol. 2004;14:618-24 pubmed
    During vertebrate embryogenesis, members of the Lefty subclass of Transforming Growth Factor-beta (TGFbeta) proteins act as extracellular antagonists of the signaling pathway for Nodal, a TGFbeta-related ligand essential for mesendoderm ..
  3. Kwon G, Viotti M, Hadjantonakis A. The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. Dev Cell. 2008;15:509-20 pubmed publisher
  4. Nakamura T, Mine N, Nakaguchi E, Mochizuki A, Yamamoto M, Yashiro K, et al. Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system. Dev Cell. 2006;11:495-504 pubmed
    ..While manipulating Nodal and Lefty gene expression, we have observed phenomena that are indicative of the involvement of a self-enhancement and ..
  5. Oki S, Hashimoto R, Okui Y, Shen M, Mekada E, Otani H, et al. Sulfated glycosaminoglycans are necessary for Nodal signal transmission from the node to the left lateral plate in the mouse embryo. Development. 2007;134:3893-904 pubmed
    ..Inhibition of sulfated GAG biosynthesis prevents Nodal expression in the LPM. These data suggest that Nodal produced at the node might travel directly to the LPM via interaction with sulfated GAGs. ..
  6. Yamamoto M, Meno C, Sakai Y, Shiratori H, Mochida K, Ikawa Y, et al. The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse. Genes Dev. 2001;15:1242-56 pubmed
    ..These results indicate that a Nodal-FoxH1 signaling pathway plays a central role in A-P patterning and node formation in the mouse. ..
  7. Meno C, Shimono A, Saijoh Y, Yashiro K, Mochida K, Ohishi S, et al. lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal. Cell. 1998;94:287-97 pubmed
    b>lefty-1, lefty-2, and nodal are expressed on the left side of developing mouse embryos and are implicated in left-right (L-R) determination. The role of lefty-1 was examined by analyzing mutant mice lacking this gene...
  8. Yamamoto M, Saijoh Y, Perea Gomez A, Shawlot W, Behringer R, Ang S, et al. Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo. Nature. 2004;428:387-92 pubmed
    ..the driving force for DVE migration by stimulating the proliferation of visceral endoderm cells, the antagonists Lefty1 and Cerl determine the direction of migration by asymmetrically inhibiting Nodal activity on the future anterior ..
  9. Oki S, Kitajima K, Marques S, Belo J, Yokoyama T, Hamada H, et al. Reversal of left-right asymmetry induced by aberrant Nodal signaling in the node of mouse embryos. Development. 2009;136:3917-25 pubmed publisher
    ..The ectopic expression of Lefty1 delays the onset of Nodal expression in the lateral plate mesoderm...
  10. Perea Gomez A, Vella F, Shawlot W, Oulad Abdelghani M, Chazaud C, Meno C, et al. Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. Dev Cell. 2002;3:745-56 pubmed
    ..Here, we demonstrate that Cerberus-like(-/-);Lefty1(-/-) compound mutants can develop a primitive streak ectopically in the embryo...
  11. Brennan J, Lu C, Norris D, Rodriguez T, Beddington R, Robertson E. Nodal signalling in the epiblast patterns the early mouse embryo. Nature. 2001;411:965-9 pubmed
    ..Our experiments show that proximal-distal and subsequent anterior-posterior polarity of the pregastrulation embryo result from reciprocal cell-cell interactions between the epiblast and the two extra-embryonic tissues. ..
  12. Marques S, Borges A, Silva A, Freitas S, Cordenonsi M, Belo J. The activity of the Nodal antagonist Cerl-2 in the mouse node is required for correct L/R body axis. Genes Dev. 2004;18:2342-7 pubmed
    ..Our results demonstrate that Cerl-2 plays a key role in restricting the Nodal signaling pathway toward the left side of the mouse embryo by preventing its activity in the right side. ..
  13. Kimura Yoshida C, Nakano H, Okamura D, Nakao K, Yonemura S, Belo J, et al. Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm. Dev Cell. 2005;9:639-50 pubmed
    ..We propose that Wnt/beta-catenin signaling mediates A-P axis polarization by guiding cell migration toward the prospective anterior in the pregastrula mouse embryo...
  14. Yoshioka H, Meno C, Koshiba K, Sugihara M, Itoh H, Ishimaru Y, et al. Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry. Cell. 1998;94:299-305 pubmed
    Signaling molecules such as Activin, Sonic hedgehog, Nodal, Lefty, and Vg1 have been found to be involved in determination of left-right (L-R) asymmetry in the chick, mouse, or frog...
  15. Constam D, Robertson E. SPC4/PACE4 regulates a TGFbeta signaling network during axis formation. Genes Dev. 2000;14:1146-55 pubmed
    ..Gene expression analysis during early somite stages indicates that spc4 is genetically upstream of nodal, pitx2, lefty1, and lefty2 and perhaps maintains the balance between Nodal and BMP signaling in the lateral plate that is ..
  16. Constam D, Robertson E. Tissue-specific requirements for the proprotein convertase furin/SPC1 during embryonic turning and heart looping. Development. 2000;127:245-54 pubmed
    ..Here we show additionally that left-sided expression of pitx2 and lefty-2 are also perturbed in Furin-deficient embryos...
  17. Meno C, Saijoh Y, Fujii H, Ikeda M, Yokoyama T, Yokoyama M, et al. Left-right asymmetric expression of the TGF beta-family member lefty in mouse embryos. Nature. 1996;381:151-5 pubmed
    ..Here we report on the gene lefty, a member of the transforming growth factor-beta family, which may encode a morphogen for L-R determination...
  18. Krebs L, Iwai N, Nonaka S, Welsh I, Lan Y, Jiang R, et al. Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev. 2003;17:1207-12 pubmed
    ..Our results demonstrate that Dll1-mediated Notch signaling is essential for generation of left-right asymmetry, and that the Notch pathway acts upstream of Nodal expression during left-right asymmetry determination in mice. ..
  19. Di Stefano P, Cabodi S, Boeri Erba E, Margaria V, Bergatto E, Giuffrida M, et al. P130Cas-associated protein (p140Cap) as a new tyrosine-phosphorylated protein involved in cell spreading. Mol Biol Cell. 2004;15:787-800 pubmed
  20. Clements M, Pernaute B, Vella F, Rodriguez T. Crosstalk between Nodal/activin and MAPK p38 signaling is essential for anterior-posterior axis specification. Curr Biol. 2011;21:1289-95 pubmed publisher
    ..Collectively, our results reveal a novel role for p38 in regulating the threshold of Nodal signaling and propose a new mechanism by which A-P axis development can be reinforced during early embryogenesis. ..
  21. Pennekamp P, Karcher C, Fischer A, Schweickert A, Skryabin B, Horst J, et al. The ion channel polycystin-2 is required for left-right axis determination in mice. Curr Biol. 2002;12:938-43 pubmed
    Generation of laterality depends on a pathway which involves the asymmetrically expressed genes nodal, Ebaf, Leftb, and Pitx2. In mouse, node monocilia are required upstream of the nodal cascade...
  22. Rankin C, Bunton T, Lawler A, Lee S. Regulation of left-right patterning in mice by growth/differentiation factor-1. Nat Genet. 2000;24:262-5 pubmed
    ..In most Gdf1-/- embryos, the expression of Ebaf (formerly lefty-1) in the left side of the floor plate and Leftb (formerly lefty-2), nodal and Pitx2 in the left lateral plate ..
  23. Fiorenzano A, Pascale E, D Aniello C, Acampora D, Bassalert C, Russo F, et al. Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency. Nat Commun. 2016;7:12589 pubmed publisher
    ..All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo. ..
  24. Zhang L, Zhang J, Xu C, Zhou X, Wang W, Zheng R, et al. Lefty-1 alleviates TGF-β1-induced fibroblast-myofibroblast transdifferentiation in NRK-49F cells. Drug Des Devel Ther. 2015;9:4669-78 pubmed publisher
    ..The left-right determination factor (Lefty) is an important cytokine of the transforming growth factor (TGF)-β family, with two variants, Lefty-1 and ..
  25. Botilde Y, Yoshiba S, Shinohara K, Hasegawa T, Nishimura H, Shiratori H, et al. Cluap1 localizes preferentially to the base and tip of cilia and is required for ciliogenesis in the mouse embryo. Dev Biol. 2013;381:203-12 pubmed publisher
    ..Our results suggest that Cluap1 contributes to ciliogenesis by regulating the intraflagellar transport (IFT) cycle at the base and tip of the cilium. ..
  26. Ishimura A, Chida S, Osada S. Man1, an inner nuclear membrane protein, regulates left-right axis formation by controlling nodal signaling in a node-independent manner. Dev Dyn. 2008;237:3565-76 pubmed publisher
    ..Notably, Lefty1, a marker for the midline barrier, was maintained in Man1(Delta/Delta) mutants...
  27. Adachi H, Saijoh Y, Mochida K, Ohishi S, Hashiguchi H, Hirao A, et al. Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer. Genes Dev. 1999;13:1589-600 pubmed
    ..A 3. 5-kb region of nodal that contained ASE responded to mutations in iv, inv, and lefty-1, all genes that act upstream of nodal. The same 3...
  28. Guo Q, Li J. Distinct functions of the major Fgf8 spliceform, Fgf8b, before and during mouse gastrulation. Development. 2007;134:2251-60 pubmed
  29. Takeuchi J, Lickert H, Bisgrove B, Sun X, Yamamoto M, Chawengsaksophak K, et al. Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry. Proc Natl Acad Sci U S A. 2007;104:846-51 pubmed
    ..Brg1 is also required for these processes, suggesting that BAF complexes are key components of nuclear Notch signaling. We propose a critical role for Baf60c in Notch-dependent transcription and LR asymmetry. ..
  30. Oulad Abdelghani M, Chazaud C, Bouillet P, Mattei M, Dolle P, Chambon P. Stra3/lefty, a retinoic acid-inducible novel member of the transforming growth factor-beta superfamily. Int J Dev Biol. 1998;42:23-32 pubmed
    ..a novel member of the TGF-beta superfamily, corresponds to, but extends more 3' than the recently published lefty sequence (Meno et al., 1996, Nature 381:151-155)...
  31. Dai H, Wang B, Yang L, Chen J, Zhu G, Sun M, et al. TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling. Nature. 2016;538:528-532 pubmed publisher
    ..Increased Nodal signalling is probably due to diminished expression of the Lefty1 and Lefty2 genes, which encode inhibitors of Nodal signalling...
  32. Camus A, Perea Gomez A, Moreau A, Collignon J. Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo. Dev Biol. 2006;295:743-55 pubmed
  33. Aoyama M, Sun Wada G, Yamamoto A, Yamamoto M, Hamada H, Wada Y. Spatial restriction of bone morphogenetic protein signaling in mouse gastrula through the mVam2-dependent endocytic pathway. Dev Cell. 2012;22:1163-75 pubmed publisher
    ..We found that mVam2, which interacts with BMP type I receptor, is required for the spatiotemporal modulation of BMP signaling, via sequestration of the receptor complex in the late stages of the endocytic pathway...
  34. Chang H, Zwijsen A, Vogel H, Huylebroeck D, Matzuk M. Smad5 is essential for left-right asymmetry in mice. Dev Biol. 2000;219:71-8 pubmed
    ..Recent studies have implicated several TGF-beta family signaling proteins (i.e., nodal, lefty-1, lefty-2, activin receptor type IIB, and Smad2) in L-R axis determination in the mouse...
  35. Fuller K, O Connell J, Gordon J, Mauti O, EGGENSCHWILER J. Rab23 regulates Nodal signaling in vertebrate left-right patterning independently of the Hedgehog pathway. Dev Biol. 2014;391:182-95 pubmed publisher
    ..Collectively, these data suggest that Rab23 is an essential component of the mechanism that transmits asymmetric patterning information from the node to the LPM. ..
  36. Wu Q, Kanata K, Saba R, Deng C, Hamada H, Saga Y. Nodal/activin signaling promotes male germ cell fate and suppresses female programming in somatic cells. Development. 2013;140:291-300 pubmed publisher
  37. Mesnard D, Constam D. Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst. J Cell Biol. 2010;191:129-39 pubmed publisher
    ..The unprecedented sensitivity and spatial resolution of CLIP opens exciting new possibilities to elucidate PC functions in vivo. ..
  38. Komatsu Y, Kaartinen V, Mishina Y. Cell cycle arrest in node cells governs ciliogenesis at the node to break left-right symmetry. Development. 2011;138:3915-20 pubmed publisher
  39. Miura S, Singh A, Mishina Y. Bmpr1a is required for proper migration of the AVE through regulation of Dkk1 expression in the pre-streak mouse embryo. Dev Biol. 2010;341:246-54 pubmed publisher
    ..Thus, our results suggest that BMP signaling regulates the expression patterns of Dkk1 for anterior migration of the AVE. ..
  40. Zhang Z, Jiang T, Li Q, Wang J, Yang D, Li X, et al. Nodal activates smad and extracellular signal-regulated kinases 1/2 pathways promoting renal cell carcinoma proliferation. Mol Med Rep. 2015;12:587-94 pubmed publisher
    ..Expression of the nodal gene is high in a number of tumor cell types and may promote tumor growth. The expression of lefty, an inhibitor of nodal is often reduced in tumor cells...
  41. Barrott J, Cash G, Smith A, Barrow J, Murtaugh L. Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndrome. Proc Natl Acad Sci U S A. 2011;108:12752-7 pubmed publisher
    ..Conditional deletion of Porcn thus provides an experimental model of FDH, as well as a valuable tool to probe Wnt ligand function in vivo...
  42. Bonnafe E, Touka M, AitLounis A, Baas D, Barras E, Ucla C, et al. The transcription factor RFX3 directs nodal cilium development and left-right asymmetry specification. Mol Cell Biol. 2004;24:4417-27 pubmed
    ..In conclusion, RFX3 is essential for the differentiation of nodal monocilia and hence for LR body axis determination. ..
  43. Dufort D, Schwartz L, Harpal K, Rossant J. The transcription factor HNF3beta is required in visceral endoderm for normal primitive streak morphogenesis. Development. 1998;125:3015-25 pubmed
    ..We show that such mutant embryos lack foregut and midgut endoderm. In addition, left-right asymmetry is affected in the mutant embryos. ..
  44. Shiratori H, Hamada H. TGF? signaling in establishing left-right asymmetry. Semin Cell Dev Biol. 2014;32:80-4 pubmed publisher
    Two TGF?-related proteins, Nodal and Lefty, are asymmetrically expressed and play central roles in establishing left-right (L-R) asymmetry of our body...
  45. King T, Brown N. Embryonic asymmetry: the left side gets all the best genes. Curr Biol. 1999;9:R18-22 pubmed
  46. Spiller C, Feng C, Jackson A, Gillis A, Rolland A, Looijenga L, et al. Endogenous Nodal signaling regulates germ cell potency during mammalian testis development. Development. 2012;139:4123-32 pubmed publisher
    ..Thus, Nodal signaling provides a molecular control mechanism that regulates male germ cell potency in normal development and testicular cancer. ..
  47. Perea Gomez A, Shawlot W, Sasaki H, Behringer R, Ang S. HNF3beta and Lim1 interact in the visceral endoderm to regulate primitive streak formation and anterior-posterior polarity in the mouse embryo. Development. 1999;126:4499-511 pubmed
    ..Moreover, HNF3beta (-)(/)(-);Lim1(-)(/)(-) mutant embryos also exhibit defects in mesoderm patterning that are likely due to lack of specification of anterior primitive streak cells. ..
  48. Meno C, Takeuchi J, Sakuma R, Koshiba Takeuchi K, Ohishi S, Saijoh Y, et al. Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2. Dev Cell. 2001;1:127-38 pubmed
    ..These results suggest that Nodal is a long-range signaling molecule but that its range of action is normally limited by the feedback inhibitor Lefty2. ..
  49. Tsukui T, Capdevila J, Tamura K, Ruiz Lozano P, Rodriguez Esteban C, Yonei Tamura S, et al. Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1. Proc Natl Acad Sci U S A. 1999;96:11376-81 pubmed
    ..Expression of the left-specific gene Lefty-1 is absent in Shh(-/-) embryos, suggesting that the observed laterality defects could be the result of the lack ..
  50. Tang M, Xu Y, Julian J, Carson D, Tabibzadeh S. Lefty is expressed in mouse endometrium in estrous cycle and peri-implantation period. Hum Reprod. 2005;20:872-80 pubmed
    ..Ebaf/lefty participates in tissue remodelling of human endometrium by induction of matrix metalloproteases (MMP)...
  51. Powers S, Taniguchi K, Yen W, Melhuish T, Shen J, Walsh C, et al. Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation. Development. 2010;137:249-59 pubmed publisher
    ..Together, these data show that Tgif function is required for gastrulation, and provide the first clear evidence that Tgifs limit the transcriptional response to Nodal signaling during early embryogenesis. ..
  52. Saijoh Y, Adachi H, Mochida K, Ohishi S, Hirao A, Hamada H. Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2. Genes Dev. 1999;13:259-69 pubmed
    Both lefty-1 and lefty-2 genes are expressed on the left side of developing mouse embryos and are implicated in left-right (L-R) axis formation...
  53. Rana A, Barbera J, Rodriguez T, Lynch D, Hirst E, Smith J, et al. Targeted deletion of the novel cytoplasmic dynein mD2LIC disrupts the embryonic organiser, formation of the body axes and specification of ventral cell fates. Development. 2004;131:4999-5007 pubmed
    ..the left-right axis and for normal expression of Nodal, and the ventral neural tube fails to express Shh, Foxa2 and Ebaf. mD2LIC also functions indirectly in the survival of anterior definitive endoderm and in the maintenance of the ..
  54. Izraeli S, Lowe L, Bertness V, Good D, Dorward D, Kirsch I, et al. The SIL gene is required for mouse embryonic axial development and left-right specification. Nature. 1999;399:691-4 pubmed
    ..indicates that the consequences of abnormal midline development for left-right patterning depend on the time of onset, duration and severity of disruption of the normal asymmetric patterns of expression of nodal, lefty-2 and Pitx2.
  55. Pulina M, Hou S, Mittal A, Jülich D, Whittaker C, Holley S, et al. Essential roles of fibronectin in the development of the left-right embryonic body plan. Dev Biol. 2011;354:208-20 pubmed publisher
    ..FN is also required for the expression of Lefty 1/2 and activation of SMADs 2 and 3 at the floor plate, while cell fate specification of the notochord and the ..
  56. Nishioka N, Nagano S, Nakayama R, Kiyonari H, Ijiri T, Taniguchi K, et al. Ssdp1 regulates head morphogenesis of mouse embryos by activating the Lim1-Ldb1 complex. Development. 2005;132:2535-46 pubmed
    ..These results suggest that Ssdp1 regulates the development of late head organizer tissues and body growth by functioning as an essential activator component of a Lim1 complex through interaction with Ldb1. ..
  57. Mine N, Anderson R, Klingensmith J. BMP antagonism is required in both the node and lateral plate mesoderm for mammalian left-right axis establishment. Development. 2008;135:2425-34 pubmed publisher
    ..These results indicate that BMP antagonism is required in both the node and LPM to facilitate L-R axis establishment in the mammalian embryo. ..
  58. Pereira P, Dobreva M, Maas E, Cornelis F, Moya I, Umans L, et al. Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion. Development. 2012;139:3343-54 pubmed publisher
    ..We conclude that antagonism of Nodal signaling by BMP/Smad5 signaling prevents primitive streak formation in the amnion of normal mouse embryos. ..
  59. Sugrue K, Zohn I. Mechanism for generation of left isomerism in Ccdc40 mutant embryos. PLoS ONE. 2017;12:e0171180 pubmed publisher
    ..Ccdc40lnks mutants show delayed induction of markers of the left-lateral plate mesoderm (L-LPM) including Lefty1, Lefty2 and Nodal...
  60. Chazaud C, Rossant J. Disruption of early proximodistal patterning and AVE formation in Apc mutants. Development. 2006;133:3379-87 pubmed
    ..In addition, we found that nuclear beta-catenin and other molecular markers are asymmetrically expressed by 4.5 days. ..
  61. Acampora D, Di Giovannantonio L, Di Salvio M, Mancuso P, Simeone A. Selective inactivation of Otx2 mRNA isoforms reveals isoform-specific requirement for visceral endoderm anteriorization and head morphogenesis and highlights cell diversity in the visceral endoderm. Mech Dev. 2009;126:882-97 pubmed publisher
    ..and specification of rostral neuroectoderm at least in part by controlling the expression of Dkk1 and Lefty1. Here, we investigated the relevance of the Otx2 transcriptional control in these processes...
  62. Beckers A, Alten L, Viebahn C, Andre P, Gossler A. The mouse homeobox gene Noto regulates node morphogenesis, notochordal ciliogenesis, and left right patterning. Proc Natl Acad Sci U S A. 2007;104:15765-70 pubmed
    ..Our results establish Noto as an essential regulator of node morphogenesis and ciliogenesis in the posterior notochord, and suggest Noto acts upstream of Foxj1 and Rfx3...
  63. Field S, Riley K, Grimes D, Hilton H, Simon M, Powles Glover N, et al. Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2. Development. 2011;138:1131-42 pubmed publisher
    ..Together with co-expression in the node, these data argue that Pkd1l1 is the elusive Pkd2 binding partner required for L-R patterning and support the two-cilia hypothesis. ..
  64. Murray S, Gridley T. Snail family genes are required for left-right asymmetry determination, but not neural crest formation, in mice. Proc Natl Acad Sci U S A. 2006;103:10300-10304 pubmed publisher
  65. Houde C, Dickinson R, Houtzager V, Cullum R, Montpetit R, Metzler M, et al. Hippi is essential for node cilia assembly and Sonic hedgehog signaling. Dev Biol. 2006;300:523-33 pubmed
  66. Alten L, Schuster Gossler K, Beckers A, Groos S, Ulmer B, Hegermann J, et al. Differential regulation of node formation, nodal ciliogenesis and cilia positioning by Noto and Foxj1. Development. 2012;139:1276-84 pubmed publisher
    ..Thus, the function of Foxj1 in vertebrate organs of asymmetry is conserved, and Noto regulates node morphogenesis and the posterior localization of cilia on node cells independently of Foxj1. ..
  67. Varlet I, Collignon J, Norris D, Robertson E. Nodal signaling and axis formation in the mouse. Cold Spring Harb Symp Quant Biol. 1997;62:105-13 pubmed
  68. Furtado M, Solloway M, Jones V, Costa M, Biben C, Wolstein O, et al. BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4. Genes Dev. 2008;22:3037-49 pubmed publisher
    ..We conclude that BMP/SMAD1 signaling sets a bilateral, repressive threshold for NODAL-dependent Nodal activation in LPM, limiting availability of SMAD4. This repressive threshold is essential for bistable output of the LR system. ..
  69. Kumar A, Lualdi M, Lewandoski M, Kuehn M. Broad mesodermal and endodermal deletion of Nodal at postgastrulation stages results solely in left/right axial defects. Dev Dyn. 2008;237:3591-601 pubmed publisher
    ..No other abnormalities were found, suggesting that Nodal signaling has no additional essential functions in developmental patterning within the extensive mesodermal and endodermal domains marked by T-Cre activity. ..
  70. Chu J, Shen M. Functional redundancy of EGF-CFC genes in epiblast and extraembryonic patterning during early mouse embryogenesis. Dev Biol. 2010;342:63-73 pubmed publisher
    ..Our results indicate that both Cripto and Cryptic function non-cell-autonomously during normal development, and that most if not all Nodal activity in early mouse embryogenesis is EGF-CFC-dependent. ..
  71. Barratt K, Glanville Jones H, Arkell R. The Zic2 gene directs the formation and function of node cilia to control cardiac situs. Genesis. 2014;52:626-35 pubmed publisher
    ..Zic2 appears to be a component of the gene regulatory network that drives ciliation of node cells during gastrulation. ..
  72. Tang M, Naidu D, Hearing P, Handwerger S, Tabibzadeh S. LEFTY, a member of the transforming growth factor-beta superfamily, inhibits uterine stromal cell differentiation: a novel autocrine role. Endocrinology. 2010;151:1320-30 pubmed publisher
    b>LEFTY is expressed in normal endometrium in cells that decidualize. To understand the importance of this expression, we have studied the effect of LEFTY on decidualization in vitro and in vivo...
  73. Qiu Z, Elsayed Z, Peterkin V, Alkatib S, Bennett D, Landry J. Ino80 is essential for proximal-distal axis asymmetry in part by regulating Bmp4 expression. BMC Biol. 2016;14:18 pubmed publisher
    ..shows elevated Bmp4 expression and reduced expression of distal visceral endoderm (DVE) markers Cer1, Hex, and Lefty1. In culture, Bmp4 maintains stem cell pluripotency and when overexpressed is a known negative regulator of DVE ..
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    ..We note that the pattern of Hcfc1(epiKO/Y) lethality displays many similarities to loss of ?-catenin function. These results reveal essential new roles for HCF-1 in early embryonic cell proliferation and development. ..
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    ..Loss of rab7 function results in severe inhibition of this endocytic pathway. Our results indicate that the microautophagic process and flow of the endocytic membrane have essential roles in early embryonic development...
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    ..signaling molecules in mammals include three transforming growth factor beta (TGFbeta)-related factors, Nodal, Lefty1 and Lefty2. They are all expressed on the left half of developing mouse embryos...