Lefty2

Summary

Gene Symbol: Lefty2
Description: left-right determination factor 2
Alias: 6030463A22Rik, Ebaf, Lefta, Leftb, lefty-2, lefty-B, left-right determination factor 2, endometrial bleeding associated factor, left-right determination factor B, left-right determination, factor A
Species: mouse

Top Publications

  1. pmc 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
    T Tsukui
    The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037 1099, USA
    Proc Natl Acad Sci U S A 96:11376-81. 1999
  2. ncbi Genetic dissection of nodal function in patterning the mouse embryo
    L A Lowe
    Experimental Immunology Branch, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Development 128:1831-43. 2001
  3. ncbi Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo
    Anne Camus
    Laboratoire de Développement des Vertébrés, Institut Jacques Monod UMR 7592 CNRS, Universités Paris 6 et 7, 2 place Jussieu, 75251 Paris, France
    Dev Biol 295:743-55. 2006
  4. pmc SPC4/PACE4 regulates a TGFbeta signaling network during axis formation
    D B Constam
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138 USA
    Genes Dev 14:1146-55. 2000
  5. ncbi Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system
    Tetsuya Nakamura
    Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University and CREST SORST, Japan Science and Technology Corporation, Suita, Osaka 565 0871, Japan
    Dev Cell 11:495-504. 2006
  6. ncbi Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2
    Y Saijoh
    Division of Molecular Biology, Osaka University, Japan
    Mol Cell 5:35-47. 2000
  7. ncbi 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
    C Meno
    Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan
    Genes Cells 2:513-24. 1997
  8. ncbi Tissue-specific requirements for the proprotein convertase furin/SPC1 during embryonic turning and heart looping
    D B Constam
    Harvard University, Department of Molecular Biology, Cambridge, MA 02138, USA
    Development 127:245-54. 2000
  9. doi Bicaudal C, a novel regulator of Dvl signaling abutting RNA-processing bodies, controls cilia orientation and leftward flow
    Charlotte Maisonneuve
    Ecole Polytechnique Federale de Lausanne, Station 19, Lausanne, Switzerland
    Development 136:3019-30. 2009
  10. ncbi Left-right patterning of the mouse lateral plate requires nodal produced in the node
    Yukio Saijoh
    Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1 3 Yamada oka, Osaka 565 0871, Suita, Japan
    Dev Biol 256:160-72. 2003

Scientific Experts

  • Hidetaka Shiratori
  • Yukio Saijoh
  • W J Weninger
  • Stephane D Vincent
  • Amer Ahmed Rana
  • Paolo Cinelli
  • Elizabeth J Robertson
  • Hiroshi Hamada
  • Daniel B Constam
  • Isabelle Migeotte
  • C Meno
  • Kathryn V Anderson
  • Shinya Oki
  • Dominic P Norris
  • Daniel Mesnard
  • Daniela D'Andrea
  • Giovanna L Liguori
  • Haixia Ma
  • Naoki Mine
  • Jose Antonio Belo
  • Sara Marques
  • Chikara Meno
  • H Hamada
  • Quan Wu
  • Mardi J Sutherland
  • Wenqing Cai
  • Minako Aoyama
  • X M Zhang
  • Christine E Larkins
  • Cassy M Spiller
  • Manuel Viotti
  • Joshua Bloomekatz
  • Mary C Trask
  • Joaquim Grego-Bessa
  • Melanie Clements
  • Sarah Field
  • Yoshihiro Komatsu
  • William E Dowdle
  • Maria V Pulina
  • Tania Attie-Bitach
  • Nicholas Katsanis
  • Yumiko Saga
  • Jeffrey D Lee
  • Aitana Perea-Gomez
  • Luis C Fernandez-Diaz
  • Heli Jokela
  • Hai Song
  • D B Constam
  • A Perea-Gomez
  • Doris Kinzel
  • Philipp Andre
  • Charlotte Maisonneuve
  • Heiko Lickert
  • Charisios D Tsiairis
  • Masamichi Yamamoto
  • Wolfgang Wurst
  • Yuji Mishina
  • Milena B Furtado
  • Amit Kumar
  • Akihiko Ishimura
  • Jane Brennan
  • Nikolas Uez
  • Kenryo Furushima
  • John Klingensmith
  • Qiuxia Guo
  • Chiharu Kimura-Yoshida
  • Shinichi Aizawa
  • Jeanette Vierkotten
  • Caroline Houde
  • Tetsuya Nakamura
  • Anne Camus
  • Shigeto Miura
  • Stephen A Murray
  • Nadav Ben-Haim
  • Christina D Cota
  • Ana Cristina Borges
  • Martin Hrabe de Angelis
  • Martin Blum
  • L A Lowe
  • J Ann Le Good
  • Michael M Shen
  • Bradley J Merrill
  • K Mochida
  • E Bonnafe
  • S Ohishi
  • Olivia G Kelly
  • Min Zhang
  • Simon D Bamforth
  • E Tian
  • Zhen Ao Zhao

Detail Information

Publications97

  1. pmc 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
    T Tsukui
    The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037 1099, USA
    Proc Natl Acad Sci U S A 96:11376-81. 1999
    ..Thus, the roles of Shh and RA in left-right specification indeed are conserved among vertebrates, and the Shh and RA pathways converge in the control of Lefty-1...
  2. ncbi Genetic dissection of nodal function in patterning the mouse embryo
    L A Lowe
    Experimental Immunology Branch, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Development 128:1831-43. 2001
    ..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...
  3. ncbi Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo
    Anne Camus
    Laboratoire de Développement des Vertébrés, Institut Jacques Monod UMR 7592 CNRS, Universités Paris 6 et 7, 2 place Jussieu, 75251 Paris, France
    Dev Biol 295:743-55. 2006
    ....
  4. pmc SPC4/PACE4 regulates a TGFbeta signaling network during axis formation
    D B Constam
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138 USA
    Genes Dev 14:1146-55. 2000
    ..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 critical for L/R ..
  5. ncbi Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system
    Tetsuya Nakamura
    Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University and CREST SORST, Japan Science and Technology Corporation, Suita, Osaka 565 0871, Japan
    Dev Cell 11:495-504. 2006
    ..Nodal and Lefty are deployed as a SELI system required to amplify this initial bias and convert it into robust asymmetry...
  6. ncbi Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2
    Y Saijoh
    Division of Molecular Biology, Osaka University, Japan
    Mol Cell 5:35-47. 2000
    The left-right (L-R) asymmetric expression of lefty2 and nodal is controlled by a left side-specific enhancer (ASE)...
  7. ncbi 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
    C Meno
    Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan
    Genes Cells 2:513-24. 1997
    ..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...
  8. ncbi Tissue-specific requirements for the proprotein convertase furin/SPC1 during embryonic turning and heart looping
    D B Constam
    Harvard University, Department of Molecular Biology, Cambridge, MA 02138, USA
    Development 127:245-54. 2000
    ..Overall, we conclude that Furin activity is essential in both extraembryonic and precardiac mesoderm, and in definitive endoderm derivatives...
  9. doi Bicaudal C, a novel regulator of Dvl signaling abutting RNA-processing bodies, controls cilia orientation and leftward flow
    Charlotte Maisonneuve
    Ecole Polytechnique Federale de Lausanne, Station 19, Lausanne, Switzerland
    Development 136:3019-30. 2009
    ..These results suggest a model whereby BicC links the orientation of cilia with PCP, possibly by regulating RNA silencing in P-bodies...
  10. ncbi Left-right patterning of the mouse lateral plate requires nodal produced in the node
    Yukio Saijoh
    Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1 3 Yamada oka, Osaka 565 0871, Suita, Japan
    Dev Biol 256:160-72. 2003
    ..Conversely, ectopic expression of the Nodal inhibitor Lefty2 in the node of Nodal(neo/+) embryos resulted in a phenotype similar to that of the Nodal(neo/neo) mutant...
  11. ncbi Extraembryonic proteases regulate Nodal signalling during gastrulation
    Séverine Beck
    Developmental Biology Group, Swiss Institute for Experimental Cancer Research ISREC, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nat Cell Biol 4:981-5. 2002
    ..A lack of Spc1 and Spc4 affects both pathways because these proteases also stimulate induction of Bmp4...
  12. pmc The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse
    M Yamamoto
    Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Japan
    Genes Dev 15:1242-56. 2001
    ..These results indicate that a Nodal-FoxH1 signaling pathway plays a central role in A-P patterning and node formation in the mouse...
  13. ncbi Nodal signalling in the epiblast patterns the early mouse embryo
    J Brennan
    Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Nature 411:965-9. 2001
    ..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...
  14. ncbi Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks
    Aitana Perea-Gomez
    IGBMC CNRS INSERM, Universite Louis Pasteur, 67404 Illkirch Cedex, CU de, Strasbourg, France
    Dev Cell 3:745-56. 2002
    ..Both antagonists are also required for proper patterning of the primitive streak...
  15. pmc Nodal activity in the node governs left-right asymmetry
    Jane Brennan
    Department of Molecular and Cellular Biology, Harvard University, The Biological Laboratories, Cambridge, Massachusetts 02138, USA
    Genes Dev 16:2339-44. 2002
    ..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...
  16. ncbi Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein
    S Nonaka
    Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Japan
    Cell 95:829-37. 1998
    ....
  17. ncbi The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo
    Dominic P Norris
    Department of Molecular and Cellular Biology, Harvard University, The Biological Laboratories, Cambridge, MA 02138, USA
    Development 129:3455-68. 2002
    ..However loss of the ASE disrupts Lefty2 (Leftb) expression and causes delayed Pitx2 expression leading to late onset, relatively minor LR patterning ..
  18. ncbi lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal
    C Meno
    Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan
    Cell 94:287-97. 1998
    ..These observations suggest that the role of lefty-1 is to restrict the expression of lefty-2 and nodal to the left side, and that lefty-2 or nodal encodes a signal for "leftness."..
  19. ncbi The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4
    Nadav Ben-Haim
    Ecole Polytechnique Fédérale de Lausanne EPFL ISREC, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Dev Cell 11:313-23. 2006
    ..Based on mathematical modeling, we discuss how these sequential loops control cell fate...
  20. pmc Hippi is essential for node cilia assembly and Sonic hedgehog signaling
    Caroline Houde
    Biochemistry Department, McGill University, Montreal, Canada H3G 1Y6
    Dev Biol 300:523-33. 2006
    ....
  21. ncbi Node and midline defects are associated with left-right development in Delta1 mutant embryos
    Gerhard K H Przemeck
    GSF, Institute of Experimental Genetics, Ingolstaedter Landstr 1, D 85764 Neuherberg, Germany
    Development 130:3-13. 2003
    ..Based on expression analysis in wild-type and mutant embryos, we suggest a model, in which Notch signalling is required for the proper differentiation of node cells and node morphology...
  22. ncbi Foxj1 regulates asymmetric gene expression during left-right axis patterning in mice
    Min Zhang
    Developmental Biology Research Unit, The Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    Biochem Biophys Res Commun 324:1413-20. 2004
    ..Foxj1 thus acts early in left-right axis patterning and regulates asymmetric gene expression. This regulation does not appear to be the result of a direct interaction between Foxj1 and the genes examined...
  23. pmc Pitchfork regulates primary cilia disassembly and left-right asymmetry
    Doris Kinzel
    Institute of Stem Cell Research, Helmholtz Zentrum Munchen, 85764 Neuherberg, Germany
    Dev Cell 19:66-77. 2010
    ..Thus, the observation of a disassembly phenotype in vivo provides an entry point to understand and categorize ciliary disease. AUTHOR AUDIO:..
  24. pmc Disruption of a ciliary B9 protein complex causes Meckel syndrome
    William E Dowdle
    Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, 94158, USA
    Am J Hum Genet 89:94-110. 2011
    ..Our data indicate that B9d1 is required for normal Hh signaling, ciliogenesis, and ciliary protein localization and that B9d1 and B9d2 are essential components of a B9 protein complex, disruption of which causes MKS...
  25. pmc Pten regulates collective cell migration during specification of the anterior-posterior axis of the mouse embryo
    Joshua Bloomekatz
    Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA
    Dev Biol 364:192-201. 2012
    ..The findings suggest that Pten has an essential and general role in the control of mammalian collective cell migration...
  26. pmc Yin-Yang1 is required for epithelial-to-mesenchymal transition and regulation of Nodal signaling during mammalian gastrulation
    Mary C Trask
    Department of Veterinary and Animal Science, University of Massachusetts, Amherst, 661 North Pleasant Street, Amherst, MA 01003, United States
    Dev Biol 368:273-82. 2012
    ..Intriguingly, overexpression of Nodal and concomitant reduction of Lefty2 are observed in Yy1 cKO embryos, suggesting that YY1 is normally required for proper Nodal regulation during ..
  27. doi Spatial restriction of bone morphogenetic protein signaling in mouse gastrula through the mVam2-dependent endocytic pathway
    Minako Aoyama
    Division of Biological Science, Institute of Scientific and Industrial Research, Osaka University, 8 1 Mihogaoka, Ibaraki, Osaka 567 0047, Japan
    Dev Cell 22:1163-75. 2012
    ..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...
  28. doi Endogenous Nodal signaling regulates germ cell potency during mammalian testis development
    Cassy M Spiller
    Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
    Development 139:4123-32. 2012
    ..Thus, Nodal signaling provides a molecular control mechanism that regulates male germ cell potency in normal development and testicular cancer...
  29. pmc Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment
    Wenqing Cai
    Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    Genes Dev 27:2332-44. 2013
    ..This is the first demonstration that cues from the progenitor cell environment direct the subunit variant composition of SWI/SNF to remodel the transcriptional landscape for lineage-specific differentiation...
  30. doi TGFβ signaling in establishing left-right asymmetry
    Hidetaka Shiratori
    Graduate School of Frontier Biosciences, Osaka University, Japan Electronic address
    Semin Cell Dev Biol 32:80-4. 2014
    ..We mainly discuss observations made with mouse embryos, unless indicated otherwise. ..
  31. pmc MicroRNA-127 Promotes Mesendoderm Differentiation of Mouse Embryonic Stem Cells by Targeting Left-Right Determination Factor 2
    Haixia Ma
    From the State Key Laboratory of Stem Cell and Reproductive Biology and the Institute of Zoology, University of Chinese Academy of Sciences, Beijing 100049, China
    J Biol Chem 291:12126-35. 2016
    ..Using luciferase reporter assay, left-right determination factor 2 (Lefty2), an antagonist of nodal, is identified to be a novel target of miR-127...
  32. ncbi Loss of late primitive streak mesoderm and interruption of left-right morphogenesis in the Ednrb(s-1Acrg) mutant mouse
    I C Welsh
    The Jackson Laboratory, Bar Harbor, Maine, 04609, USA
    Dev Biol 225:151-68. 2000
    ..The expression of nodal and leftb, Tgf-beta-related genes involved in a left-determinant signaling pathway, is variably lost in the left lateral ..
  33. ncbi Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node
    X M Zhang
    Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
    Cell 105:781-92. 2001
    ..Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis.[Dedicated to Rosa Beddington, a pioneer in mammalian embryology]...
  34. ncbi Regulation of left-right patterning in mice by growth/differentiation factor-1
    C T Rankin
    Department of Molecular Biology and Genetics, Baltimore, Maryland, USA
    Nat Genet 24:262-5. 2000
    ..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 mesoderm was absent, suggesting that Gdf1 acts ..
  35. pmc Cripto promotes A-P axis specification independently of its stimulatory effect on Nodal autoinduction
    Daniela D'Andrea
    Stem Cell Fate Laboratory, Institute of Genetics and Biophysics A Buzzati Traverso, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy
    J Cell Biol 180:597-605. 2008
    ....
  36. pmc Zic3 is required in the migrating primitive streak for node morphogenesis and left-right patterning
    Mardi J Sutherland
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
    Hum Mol Genet 22:1913-23. 2013
    ....
  37. pmc Nodal/activin signaling promotes male germ cell fate and suppresses female programming in somatic cells
    Quan Wu
    Department of Genetics, SOKENDAI, Yata 1111, Mishima 411 8540, Japan
    Development 140:291-300. 2013
    ....
  38. doi Defective Nodal and Cerl2 expression in the Arl13b(hnn) mutant node underlie its heterotaxia
    Christine E Larkins
    Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA
    Dev Biol 367:15-24. 2012
    ..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...
  39. pmc Role of the gut endoderm in relaying left-right patterning in mice
    Manuel Viotti
    Developmental Biology Program, Sloan Kettering Institute, New York, New York, United States of America
    PLoS Biol 10:e1001276. 2012
    ....
  40. pmc Left-right patterning in the mouse requires Epb4.1l5-dependent morphogenesis of the node and midline
    Jeffrey D Lee
    Developmental Biology Program, Sloan Kettering Institute, 1275 York Ave, New York NY 10065, USA
    Dev Biol 346:237-46. 2010
    ..The data suggest that the assembly of the contiguous node epithelium from mesenchymal clusters requires a rapid reorganization of apical-basal polarity that depends on Lulu/Epb4.1l5...
  41. pmc Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2
    Sarah Field
    Mammalian Genetics Unit, MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire OX11 0RD, UK
    Development 138:1131-42. 2011
    ..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...
  42. pmc Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning
    Hai Song
    Developmental Genetics Section, Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA
    Nature 466:378-82. 2010
    ..Our data suggest that PCP acts earlier than the unidirectional nodal flow during bilateral symmetry breaking in vertebrates and provide insight into the functional mechanism of PCP in organizing the vertebrate tissues in development...
  43. doi Hydroxysteroid (17beta) dehydrogenase 7 activity is essential for fetal de novo cholesterol synthesis and for neuroectodermal survival and cardiovascular differentiation in early mouse embryos
    Heli Jokela
    Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN 20520 Turku, Finland
    Endocrinology 151:1884-92. 2010
    ..The septum of the atrium was also defected in the knockout mice...
  44. doi Reversal of left-right asymmetry induced by aberrant Nodal signaling in the node of mouse embryos
    Shinya Oki
    Graduate School of Medical Sciences, Kyushu University, Fukuoka 812 8582, Japan
    Development 136:3917-25. 2009
    ..In inv/inv embryos, this system may function in reverse as a result of ectopic production of Lefty, which inhibits the Nodal signal on the left side in a manner dependent on leftward nodal flow...
  45. pmc An Hh-dependent pathway in lateral plate mesoderm enables the generation of left/right asymmetry
    Charisios D Tsiairis
    Department of Molecular and Cellular Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA
    Curr Biol 19:1912-7. 2009
    ....
  46. pmc BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4
    Milena B Furtado
    Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
    Genes Dev 22:3037-49. 2008
    ..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...
  47. doi Man1, an inner nuclear membrane protein, regulates left-right axis formation by controlling nodal signaling in a node-independent manner
    Akihiko Ishimura
    The 21st Century Center of Excellence COE Program, Akita University, Akita, Japan
    Dev Dyn 237:3565-76. 2008
    ..heart abnormalities and found that the left side-specific genes responsible for left-right (LR) asymmetry, Nodal, Lefty2, and Pitx2, were expressed bilaterally in the lateral plate mesoderm and that their expression was enhanced ..
  48. doi BMP antagonism is required in both the node and lateral plate mesoderm for mammalian left-right axis establishment
    Naoki Mine
    Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    Development 135:2425-34. 2008
    ..These results indicate that BMP antagonism is required in both the node and LPM to facilitate L-R axis establishment in the mammalian embryo...
  49. pmc Expression profiling in transgenic FVB/N embryonic stem cells overexpressing STAT3
    Paolo Cinelli
    Institute of Laboratory Animal Science, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    BMC Dev Biol 8:57. 2008
    ..In a second step, STAT3-MER overexpressing cells were used to identify STAT3 pathway-related genes by expression profiling in order to identify new key-players involved in maintenance of pluripotency in ES cells...
  50. doi Cripto-independent Nodal signaling promotes positioning of the A-P axis in the early mouse embryo
    Giovanna L Liguori
    IBB Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, Campus de Gambelas, 8005 135 Faro, Portugal
    Dev Biol 315:280-9. 2008
    ..This signaling activity drives A-P axis positioning. Our results provide evidence for the existence of Cripto-independent signaling mechanisms, by which Nodal controls axis specification in the early mouse embryo...
  51. doi The absence of Prep1 causes p53-dependent apoptosis of mouse pluripotent epiblast cells
    Luis C Fernandez-Diaz
    IFOM, FIRC Institute of Molecular Oncology Foundation, IFOM IEO Campus, Via Adamello 16, Milan, Italy
    Development 137:3393-403. 2010
    ..Despite this early lethal phenotype, Prep1 is not essential for ES cell establishment. A differential embryonic expression pattern underscores the unique function of Prep1 within the Meis-Prep family...
  52. pmc Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst
    Daniel Mesnard
    Swiss Federal Institute of Technology Lausanne, School of Life Sciences, Swiss Institute for Experimental Cancer Research, CH 1015 Lausanne, Switzerland
    J Cell Biol 191:129-39. 2010
    ..The unprecedented sensitivity and spatial resolution of CLIP opens exciting new possibilities to elucidate PC functions in vivo...
  53. ncbi The transcription factor HNF3beta is required in visceral endoderm for normal primitive streak morphogenesis
    D Dufort
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5
    Development 125:3015-25. 1998
    ..We show that such mutant embryos lack foregut and midgut endoderm. In addition, left-right asymmetry is affected in the mutant embryos...
  54. pmc Essential roles of fibronectin in the development of the left-right embryonic body plan
    Maria V Pulina
    Weill Cornell Medical College, Department of Medicine, Division of Cardiology, New York, NY, USA
    Dev Biol 354:208-20. 2011
    ..Taken together, our studies demonstrate the requisite role for a structural ECM protein and its integrin receptor in the development of the left-right axis of asymmetry in vertebrates...
  55. pmc Rac1 mediates morphogenetic responses to intercellular signals in the gastrulating mouse embryo
    Isabelle Migeotte
    Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA
    Development 138:3011-20. 2011
    ..Rac1 also has essential roles in morphogenesis of the posterior notochordal plate (the node) and the midline...
  56. pmc Crosstalk between Nodal/activin and MAPK p38 signaling is essential for anterior-posterior axis specification
    Melanie Clements
    Molecular Embryology Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK
    Curr Biol 21:1289-95. 2011
    ..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...
  57. pmc Cell cycle arrest in node cells governs ciliogenesis at the node to break left-right symmetry
    Yoshihiro Komatsu
    Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, 1011 North University Avenue, Ann Arbor, MI 48109 1078, USA
    Development 138:3915-20. 2011
    ....
  58. ncbi Mouse Lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation
    C Meno
    Division of Molecular Biology, Osaka University, Japan
    Mol Cell 4:287-98. 1999
    Mammalian lefty and zebrafish antivin form a subgroup of the TGF beta superfamily. We report that mouse mutants for lefty2 have an expanded primitive streak and form excess mesoderm, a phenotype opposite to that of mutants for the TGF ..
  59. ncbi HNF3beta and Lim1 interact in the visceral endoderm to regulate primitive streak formation and anterior-posterior polarity in the mouse embryo
    A Perea-Gomez
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM Universite Louis Pasteur, BP163, CU de Strasbourg, France
    Development 126:4499-511. 1999
    ..Moreover, HNF3beta (-)(/)(-);Lim1(-)(/)(-) mutant embryos also exhibit defects in mesoderm patterning that are likely due to lack of specification of anterior primitive streak cells...
  60. ncbi The SIL gene is required for mouse embryonic axial development and left-right specification
    S Izraeli
    Genetics Department, Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20889 5105, USA
    Nature 399:691-4. 1999
    ....
  61. ncbi The role of the brachyury gene in heart development and left-right specification in the mouse
    T King
    Department of Anatomy and Developmental Biology, St George s Hospital Medical School, London, UK
    Mech Dev 79:29-37. 1998
    ..These results implicate the node as a source of instructive signals driving expression of nodal and lefty-2 in the left lateral plate mesoderm, and being required for normal looping and situs of the heart...
  62. pmc Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis
    S Takeda
    Department of Cell Biology and Anatomy, University of Tokyo, Graduate School of Medicine, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 0033 Japan
    J Cell Biol 145:825-36. 1999
    ..These results suggest that KIF3A might be involved in mesodermal patterning and in turn neurogenesis...
  63. ncbi The ion channel polycystin-2 is required for left-right axis determination in mice
    Petra Pennekamp
    Universitatsklinikum Munster, Institut fur Humangenetik, Vesaliusweg 12 14, Germany
    Curr Biol 12:938-43. 2002
    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...
  64. ncbi Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway
    Simon D Bamforth
    Department of Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK
    Nat Genet 36:1189-96. 2004
    ..Cited2(-/-) mice lack expression of the Nodal target genes Pitx2c, Nodal and Ebaf in the left lateral plate mesoderm, where they are required for establishing laterality and cardiovascular ..
  65. ncbi Rotatin is a novel gene required for axial rotation and left-right specification in mouse embryos
    Anja M Faisst
    Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany
    Mech Dev 113:15-28. 2002
    ..In the mouse, the lateral asymmetry of the body axis is revealed first by the asymmetric expression of nodal, lefty2 and pitx2 in the left lateral plate mesoderm of the neurulating embryo...
  66. ncbi 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
    Takeshi Fujiwara
    Howard Hughes Medical Institute and Department of Cell Biology, Vanderbilt University Medical Center, 1161 21st Ave South, Nashville, TN 37232 2175, USA
    Development 129:4685-96. 2002
    ..In the absence of embryonic Bmp4, the expression of left-side determinants such as Nodal and Lefty2 is absent in the left lateral plate mesoderm (LPM)...
  67. ncbi Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node
    X M Zhang
    Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
    Cell 106:781-92. 2001
    ..Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis...
  68. ncbi Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse
    K Niederreither
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM ULP College de France, 67404 Illkirch Cedex, CU de Strasbourg, France
    Development 128:1019-31. 2001
    ..However, cardiac neural crest cells cannot be properly rescued in Raldh2(-/- )embryos, leading to outflow tract septation defects...
  69. ncbi Inhibition of excess nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1
    Rabah Iratni
    Howard Hughes Medical Institute and Department of Biochemistry, Division of Nucleic Acids Enzymology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Science 298:1996-9. 2002
    ..We propose that DRAP1 limits the spread of a morphogenetic signal by down-modulating the response to the Nodal autoregulatory loop...
  70. ncbi Otx2 is required for visceral endoderm movement and for the restriction of posterior signals in the epiblast of the mouse embryo
    A Perea-Gomez
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM Universite Louis Pasteur, BP163, 67404 Illkirch Cedex, C U de Strasbourg, France
    Development 128:753-65. 2001
    ....
  71. ncbi Tcf3: a transcriptional regulator of axis induction in the early embryo
    Bradley J Merrill
    Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021, USA
    Development 131:263-74. 2004
    ..expression of Foxa2, an axial mesoderm gene involved in node specification, with a concomitant reduction in Lefty2, a marker for lateral mesoderm...
  72. ncbi Asymmetric Nodal expression in the mouse is governed by the combinatorial activities of two distinct regulatory elements
    Stephane D Vincent
    Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
    Mech Dev 121:1403-15. 2004
    ..Our findings point to the existence of two independent pathways that control Nodal expression in the left LPM...
  73. ncbi Sulfated glycosaminoglycans are necessary for Nodal signal transmission from the node to the left lateral plate in the mouse embryo
    Shinya Oki
    Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation JST Yamada oka, Suita, Osaka 565 0871, Japan
    Development 134:3893-904. 2007
    ..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...
  74. ncbi Two nodal-responsive enhancers control left-right asymmetric expression of Nodal
    Yukio Saijoh
    Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation JST, Suita, Osaka 565 08, Japan
    Dev Dyn 232:1031-6. 2005
    ..However, the mutant mouse lacking LSE does not show obvious L-R patterning defects. These results suggest that Nodal expression in the left LPM is induced by a combination of two Nodal-responsive autoregulatory enhancers, ASE and LSE...
  75. ncbi Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development
    Wolfgang J Weninger
    Integrative Morphology Group, Department of Anatomy, University of Vienna, Waehringerstrasse 13, A 1090 Vienna, Austria
    Development 132:1337-48. 2005
    ..We show by gene expression analysis that Cited2 acts upstream of Nodal, Lefty2 and Pitx2 in the lateral mesoderm, and of Lefty1 in the presumptive floor plate...
  76. ncbi BMP signaling in the epiblast is required for proper recruitment of the prospective paraxial mesoderm and development of the somites
    Shigeto Miura
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, MD C4 10, C458, Research Triangle Park, NC 27709, USA
    Development 133:3767-75. 2006
    ..This suggests that BMP and FGF signaling function antagonistically during paraxial mesoderm development...
  77. ncbi MesP1 and MesP2 are essential for the development of cardiac mesoderm
    S Kitajima
    Cellular and Molecular Toxicology Division, National Institute of Health Sciences, Setagaya Ku, Tokyo 158 8501, Japan
    Development 127:3215-26. 2000
    ..These results strongly indicate that the defect in the cranial-cardiac mesoderm is cell-autonomous, whereas the defect in the paraxial mesoderm is a non-cell-autonomous secondary consequence...
  78. ncbi Smad5 is essential for left-right asymmetry in mice
    H Chang
    Department of Pathology, Program in Developmental Biology, Houston, Texas, 77030, USA
    Dev Biol 219:71-8. 2000
    ..These data suggest that Smad5 is upstream of lefty-1, nodal, and lefty-2, and as a consequence also of Pitx2, and Smad5 is essential for L-R axis determination...
  79. pmc Distinct functions of the major Fgf8 spliceform, Fgf8b, before and during mouse gastrulation
    Qiuxia Guo
    Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
    Development 134:2251-60. 2007
    ....
  80. pmc Crucial roles of Foxa2 in mouse anterior-posterior axis polarization via regulation of anterior visceral endoderm-specific genes
    Chiharu Kimura-Yoshida
    Department of Molecular Embryology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, Murodo cho, Izumi, Osaka 594 1101, Japan
    Proc Natl Acad Sci U S A 104:5919-24. 2007
    ..These findings provide profound insights into conserved roles of Foxa2 transcription factors in anterior specification throughout the evolution of the chordate body plan...
  81. pmc Snail family genes are required for left-right asymmetry determination, but not neural crest formation, in mice
    Stephen A Murray
    The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Proc Natl Acad Sci U S A 103:10300-4. 2006
    ....
  82. ncbi Mice with mutations in Mahogunin ring finger-1 (Mgrn1) exhibit abnormal patterning of the left-right axis
    Christina D Cota
    Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, USA
    Dev Dyn 235:3438-47. 2006
    ..Our work identifies a novel role for MGRN1 in embryonic patterning and suggests that the ubiquitination of MGRN1 target genes is essential for the proper establishment and/or maintenance of the LR axis...
  83. pmc The transcription factor RFX3 directs nodal cilium development and left-right asymmetry specification
    E Bonnafe
    Centre de Genetique Moleculaire et Cellulaire, CNRS UMR 5534, Universite Claude Bernard Lyon 1, F 69622 Villeurbanne, France
    Mol Cell Biol 24:4417-27. 2004
    ..In conclusion, RFX3 is essential for the differentiation of nodal monocilia and hence for LR body axis determination...
  84. ncbi Ftm is a novel basal body protein of cilia involved in Shh signalling
    Jeanette Vierkotten
    Institut für Entwicklungs und Molekularbiologie der Tiere EMT, Heinrich Heine Universitat, 40225 Dusseldorf, Germany
    Development 134:2569-77. 2007
    ..Furthermore, the absence of Ftm in arthropods underlines the divergence between vertebrate and Drosophila Hh pathways...
  85. ncbi Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2
    C Meno
    Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Japan
    Dev Cell 1:127-38. 2001
    The role of Lefty2 in left-right patterning was investigated by analysis of mutant mice that lack asymmetric expression of lefty2. These animals exhibited various situs defects including left isomerism...
  86. ncbi Mouse homologues of Shisa antagonistic to Wnt and Fgf signalings
    Kenryo Furushima
    Laboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology CDB, RIKEN Kobe, 2 2 3 Minatojima minami, Chuo Ku, Kobe 650 0047, Japan
    Dev Biol 306:480-92. 2007
    ....
  87. pmc Broad mesodermal and endodermal deletion of Nodal at postgastrulation stages results solely in left/right axial defects
    Amit Kumar
    Laboratory of Protein Dynamics and Signaling, National Cancer Institute, NCI Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    Dev Dyn 237:3591-601. 2008
    ..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...
  88. ncbi Differences in left-right axis pathways in mouse and chick: functions of FGF8 and SHH
    E N Meyers
    Department of Anatomy and Program in Developmental Biology, School of Medicine, and Department of Pediatrics, School of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA
    Science 285:403-6. 1999
    ..In the mouse FGF8 is a left determinant and Sonic Hedgehog is required to prevent left determinants from being expressed on the right...
  89. doi Sall4 isoforms act during proximal-distal and anterior-posterior axis formation in the mouse embryo
    Nikolas Uez
    Helmholtz Center Munich, Institute of Developmental Genetics, Ingolstaedter Landstrasse 1, Munich, Neuherberg, Germany
    Genesis 46:463-77. 2008
    ..This observation was supported through genetic interaction with beta-catenin mutants, since compound heterozygous mutants recapitulated the defects of Wnt3a mutants in posterior development...
  90. pmc Control of early anterior-posterior patterning in the mouse embryo by TGF-beta signalling
    Elizabeth J Robertson
    Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
    Philos Trans R Soc Lond B Biol Sci 358:1351-7; discussion 1357. 2003
    ....
  91. ncbi Targeted deletion of the novel cytoplasmic dynein mD2LIC disrupts the embryonic organiser, formation of the body axes and specification of ventral cell fates
    Amer Ahmed Rana
    Division of Mammalian Development, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Development 131:4999-5007. 2004
    ..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 ..
  92. pmc Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation
    Y T Yan
    Center for Advanced Biotechnology and Medicine CABM and Department of Pediatrics, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Genes Dev 13:2527-37. 1999
    ..In both Cryptic and oep mutant embryos, L-R asymmetric expression of Nodal/cyclops, Lefty2/antivin, and Pitx2 does not occur in the lateral plate mesoderm, while in Cryptic mutants Lefty1 expression is ..
  93. ncbi A role of the cryptic gene in the correct establishment of the left-right axis
    U Gaio
    Max Delbrück Centrum for Molecular Medicine, Berlin, 13125, Germany
    Curr Biol 9:1339-42. 1999
    ..Our results provide genetic evidence for a role of cryptic in the signalling cascade that determines left-right asymmetry...
  94. ncbi Retinoic acid affects left-right patterning
    S Wasiak
    Department of Molecular Biology, Universite de Montreal, Montreal, Quebec, Canada
    Dev Biol 215:332-42. 1999
    ..These events are likely to underlie the perturbations of heart looping provoked by excess RA and suggest a means by which retinoids influence the early steps in establishment of the left-right embryonic axis...
  95. ncbi The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice
    Olivia G Kelly
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720 3200, USA
    Development 131:2803-15. 2004
    ..The effect of reducing, but not eliminating, Wnt signaling in Lrp5(+/-);Lrp6(-/-) mutant embryos provides important insight into the interplay between Wnt, Fgf and Nodal signals in patterning the early mouse embryo...
  96. pmc The activity of the Nodal antagonist Cerl-2 in the mouse node is required for correct L/R body axis
    Sara Marques
    Instituto Gulbenkian de Ciencia, 2781 901 Oeiras, Portugal
    Genes Dev 18:2342-7. 2004
    ..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...
  97. ncbi Visceral endoderm mediates forebrain development by suppressing posteriorizing signals
    C Kimura
    Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2 2 1, Kumamoto, 860 0811, Japan
    Dev Biol 225:304-21. 2000
    ..These results suggest that distal visceral endoderm cells move to the future anterior side to generate a prospective forebrain territory indirectly, by preventing posteriorizing signals...