Nkx2-5

Summary

Gene Symbol: Nkx2-5
Description: NK2 homeobox 5
Alias: Csx, Nkx-2.5, Nkx2.5, tinman, homeobox protein Nkx-2.5, Drosophila NK2 transcription factor related, locus 5, NK2 transcription factor related, locus 5, cardiac-specific homeobox, homeobox protein CSX, homeobox protein NK-2 homolog E
Species: mouse

Top Publications

  1. ncbi A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease
    B G Bruneau
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell 106:709-21. 2001
  2. ncbi GATA4 transcription factor is required for ventral morphogenesis and heart tube formation
    C T Kuo
    Department of Medicine, The University of Chicago, Illinois 60637, USA
    Genes Dev 11:1048-60. 1997
  3. pmc Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth
    Izhak Kehat
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, and Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229 3039, USA
    Circ Res 108:176-83. 2011
  4. ncbi Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5
    C Biben
    Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Circ Res 87:888-95. 2000
  5. pmc Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C
    Q Lin
    Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 9148, USA
    Science 276:1404-7. 1997
  6. ncbi Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability
    Toru Oka
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Ohio 45229 3039, USA
    Circ Res 98:837-45. 2006
  7. ncbi Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development
    Matthew M Goddeeris
    Departments of Cell Biology and Pediatrics, Neonatal Perinatal Research Institute, Duke University Medical Center, Durham, NC 27710, USA
    Development 134:1593-604. 2007
  8. ncbi Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization
    Nicola Smart
    Molecular Medicine Unit, UCL Institute of Child Health, London WC1N 1EH, UK
    Nature 445:177-82. 2007
  9. ncbi Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development
    Rudiger J Blaschke
    Human Genetics, University of Heidelberg, Heidelberg, Germany
    Circulation 115:1830-8. 2007
  10. pmc GATA4 is a direct transcriptional activator of cyclin D2 and Cdk4 and is required for cardiomyocyte proliferation in anterior heart field-derived myocardium
    Anabel Rojas
    Genentech Hall, 600 16th Street, Mail Code 2240, University of California, San Francisco, San Francisco, CA 94158 2517, USA
    Mol Cell Biol 28:5420-31. 2008

Research Grants

Scientific Experts

Detail Information

Publications146 found, 100 shown here

  1. ncbi A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease
    B G Bruneau
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell 106:709-21. 2001
    ....
  2. ncbi GATA4 transcription factor is required for ventral morphogenesis and heart tube formation
    C T Kuo
    Department of Medicine, The University of Chicago, Illinois 60637, USA
    Genes Dev 11:1048-60. 1997
    ..However, they define a critical role for GATA4 in regulating the rostral-to-caudal and lateral-to-ventral folding of the embryo that is needed for normal cardiac morphogenesis...
  3. pmc Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth
    Izhak Kehat
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, and Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229 3039, USA
    Circ Res 108:176-83. 2011
    ..The signaling pathways that control eccentric versus concentric heart growth are not well understood...
  4. ncbi Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5
    C Biben
    Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Circ Res 87:888-95. 2000
    ..Our data demonstrate that the complex effects of Nkx2-5 haploinsufficiency in mice are weaker but convergent with those in humans. As in the mouse, the phenotype of human NKX2-5 mutations may be modulated by interacting alleles...
  5. pmc Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C
    Q Lin
    Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 9148, USA
    Science 276:1404-7. 1997
    ..Thus, MEF2C is an essential regulator of cardiac myogenesis and right ventricular development...
  6. ncbi Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability
    Toru Oka
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Ohio 45229 3039, USA
    Circ Res 98:837-45. 2006
    ..Thus, GATA4 is a necessary regulator of cardiac gene expression, hypertrophy, stress-compensation, and myocyte viability...
  7. ncbi Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development
    Matthew M Goddeeris
    Departments of Cell Biology and Pediatrics, Neonatal Perinatal Research Institute, Duke University Medical Center, Durham, NC 27710, USA
    Development 134:1593-604. 2007
    ..Disruption of any of these steps can result in a single OFT phenotype...
  8. ncbi Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization
    Nicola Smart
    Molecular Medicine Unit, UCL Institute of Child Health, London WC1N 1EH, UK
    Nature 445:177-82. 2007
    ....
  9. ncbi Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development
    Rudiger J Blaschke
    Human Genetics, University of Heidelberg, Heidelberg, Germany
    Circulation 115:1830-8. 2007
    ..Here, we report on a highly restricted expression pattern of the homeodomain transcription factor Shox2 in the sinus venosus myocardium, including the sinoatrial nodal region and the venous valves...
  10. pmc GATA4 is a direct transcriptional activator of cyclin D2 and Cdk4 and is required for cardiomyocyte proliferation in anterior heart field-derived myocardium
    Anabel Rojas
    Genentech Hall, 600 16th Street, Mail Code 2240, University of California, San Francisco, San Francisco, CA 94158 2517, USA
    Mol Cell Biol 28:5420-31. 2008
    ..These findings establish Cyclin D2 and Cdk4 as direct transcriptional targets of GATA4 and support a model in which GATA4 controls cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes...
  11. ncbi The splanchnic mesodermal plate directs spleen and pancreatic laterality, and is regulated by Bapx1/Nkx3.2
    Jacob Hecksher-Sørensen
    Comparative and Developmental Genetics Section, MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
    Development 131:4665-75. 2004
    ..We conclude that the SMP is an organiser responsible for the leftward growth of the spleno-pancreatic region and that Bapx1 regulates SMP functions required for pancreatic laterality...
  12. doi WNT signaling promotes Nkx2.5 expression and early cardiomyogenesis via downregulation of Hdac1
    Zhiqiang Liu
    Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing, 100191, China
    Biochim Biophys Acta 1793:300-11. 2009
    ..Our data suggest that WNT signaling pathway plays important roles in the regulation of Hdac1 during the early stage of cardiomyocyte differentiation and that the downregulation of Hdac1 promotes cardiac differentiation...
  13. ncbi Nkx-2.5 gene induction in mice is mediated by a Smad consensus regulatory region
    Christine M Liberatore
    Division of Molecular Cardiovascular Biology, The Children s Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
    Dev Biol 244:243-56. 2002
    ..where Dpp signaling mediated by the Smad homologues Mad and Medea directly regulates early cardiac expression of tinman. A conserved cluster of Smad consensus binding sequences was identified in early cardiac regulatory sequences of ..
  14. ncbi NK-2 class homeobox genes and pharyngeal/oral patterning: Nkx2-3 is required for salivary gland and tooth morphogenesis
    Christine Biben
    Victor Chang Cardiac Research Institute, St Vincent s Hospital, Darlinghurst, NSW, Australia
    Int J Dev Biol 46:415-22. 2002
    ..These data suggest roles for Nkx2-3 during pharyngeal organogenesis, although the considerable potential for genetic redundancy within and outside of this gene family may mask earlier functions in organ specification...
  15. pmc Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts
    Frank Baur
    Institut fur Molekularbiologie und Tumorforschung, Philipps Universitat Marburg, Marburg, Germany
    PLoS ONE 5:e9587. 2010
    ..Despite its close similarity to Sp1, Sp3 and Sp4, Sp2 does not bind to DNA or activate transcription when expressed in mammalian cell lines. The expression pattern and the biological relevance of Sp2 in the mouse are unknown...
  16. pmc Essential roles of ECAT15-2/Dppa2 in functional lung development
    Tomonori Nakamura
    Center for iPS Cell Research and Application CiRA, Kyoto University, Kyoto 606 8507, Japan
    Mol Cell Biol 31:4366-78. 2011
    ..These data suggest that ECAT15-2 has important roles in lung development, where it is no longer expressed, by leaving epigenetic marks from earlier developmental stages...
  17. ncbi Conditional mutagenesis of the murine serum response factor gene blocks cardiogenesis and the transcription of downstream gene targets
    Zhiyv Niu
    Center for Cardiovascular Development, Division of Cardiovascular Sciences, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030, USA
    J Biol Chem 280:32531-8. 2005
    ....
  18. ncbi Activation of the cardiac alpha-actin promoter depends upon serum response factor, Tinman homologue, Nkx-2.5, and intact serum response elements
    C Y Chen
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Dev Genet 19:119-30. 1996
    A murine cardiac specific homeoboxgene, Nkx-2.5/CSX, a potential Drosophila tinman homologue, may have a fundamental role in cardiac myocyte differentiation. DNA binding targets for Nkx-2...
  19. ncbi An enhancer sequence directs LacZ expression to developing pharyngeal endoderm in transgenic mice
    H Parmar
    Genesis 31:57-63. 2001
    ..5 showed colocalization with the LacZ-positive cells in the foregut and pharyngeal endoderm. This novel enhancer provides a means of tracking the morphogenetic movement of endodermal cells fated to form the foregut...
  20. ncbi Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart
    Haruhiro Toko
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1 8 1 Inohana, Chuo Ku, Chiba 260 8670, Japan
    J Biol Chem 277:24735-43. 2002
    b>Csx/Nkx2-5, which is essential for cardiac development of the embryo, is abundantly expressed in the adult heart. We here examined the role of Csx/Nkx2-5 in the adult heart using two kinds of transgenic mice...
  21. ncbi Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis
    Paul D Gottlieb
    Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA
    Nat Genet 31:25-32. 2002
    ..These results indicate that m-Bop is essential for cardiomyocyte differentiation and cardiac morphogenesis...
  22. ncbi A mouse model of congenital heart disease: cardiac arrhythmias and atrial septal defect caused by haploinsufficiency of the cardiac transcription factor Csx/Nkx2.5
    M Tanaka
    Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    Cold Spring Harb Symp Quant Biol 67:317-25. 2002
  23. ncbi Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart
    Kazuko Koshiba-Takeuchi
    Programs in Cardiovascular Research, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    Nat Genet 38:175-83. 2006
    ..Thus, a positive and negative feed-forward circuit between Tbx5 and Sall4 ensures precise patterning of embryonic limb and heart and provides a unifying mechanism for heart/hand syndromes...
  24. ncbi Tbx1 affects asymmetric cardiac morphogenesis by regulating Pitx2 in the secondary heart field
    Sonja Nowotschin
    Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Development 133:1565-73. 2006
    ..5. The results presented in this study unravel a novel Tbx1-Pitx2 pathway linking Tbx1 to asymmetric cardiac morphogenesis...
  25. pmc Myocardial smad4 is essential for cardiogenesis in mouse embryos
    Lanying Song
    Department of Genetics, Division of Genetic and Translational Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Circ Res 101:277-85. 2007
    ..In conclusion, this study provides the first mouse model showing that Smad4 plays essential roles during cardiogenesis...
  26. pmc Identification of cardiac-specific myosin light chain kinase
    Jason Y Chan
    Department of Physiology and Functional Genomics, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32610 0274, USA
    Circ Res 102:571-80. 2008
    ..Both overexpression and knockdown of cardiac MLCK in cultured cardiomyocytes revealed that cardiac MLCK is likely a new regulator of MLC2 phosphorylation, sarcomere organization, and cardiomyocyte contraction...
  27. pmc Foxp1 coordinates cardiomyocyte proliferation through both cell-autonomous and nonautonomous mechanisms
    Yuzhen Zhang
    Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Genes Dev 24:1746-57. 2010
    ..These data show that Foxp1 coordinates the balance of cardiomyocyte proliferation and differentiation through cell lineage-specific regulation of Fgf ligand and Nkx2.5 expression...
  28. ncbi Building the heart piece by piece: modularity of cis-elements regulating Nkx2-5 transcription
    R J Schwartz
    Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Development 126:4187-92. 1999
    Heart formation in Drosophila is dependent on the homeobox gene tinman. The homeobox gene Nkx2-5 is closely related to tinman and is the earliest known marker for cardiogenesis in vertebrate embryos...
  29. ncbi A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2
    E C Svensson
    Department of Medicine, University of Chicago, Chicago, Illinois, USA
    Nat Genet 25:353-6. 2000
    ..Our findings indicate the importance of Zfpm2 in the normal looping and septation of the heart and suggest a genetic basis for the syndrome of tricuspid atresia...
  30. ncbi FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium
    S G Tevosian
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cell 101:729-39. 2000
    ..Our findings provide the molecular inroad into the induction of coronary vasculature by myocardium in the developing heart...
  31. pmc The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis
    Manabu Shirai
    Department of Developmental Biology and Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari, Japan
    J Clin Invest 110:177-84. 2002
    ..In Rae28(-/-) embryos, expression of the cardiac selector gene Nkx2.5/Csx (Nkx2.5) was initiated properly but was not sufficiently sustained later in development...
  32. ncbi Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3'UTR-ires-Cre allele of the homeobox gene Nkx2-5
    Edouard G Stanley
    Victor Chang Cardiac Research Institute, St Vincent s Hospital, Darlinghurst, NSW, Australia
    Int J Dev Biol 46:431-9. 2002
    ..Our data suggest that the Nkx2-5IRESCre strain will be useful for genetic dissection of the multiple tiers of lineage allocation to the forming heart as well as of molecular interactions within the heart fields and heart tube...
  33. ncbi Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm
    Heiko Lickert
    Department of Molecular Embryology, Max Planck Institute for Immunobiology, Stuebeweg 51, D 79108 Freiburg, Germany
    Dev Cell 3:171-81. 2002
    ..We provide evidence that ablation of beta-catenin in embryonic endoderm changes cell fate from endoderm to precardiac mesoderm, consistent with the existence of bipotential mesendodermal progenitors in mouse embryos...
  34. ncbi Early stage-specific inhibitions of cardiomyocyte differentiation and expression of Csx/Nkx-2.5 and GATA-4 by phosphatidylinositol 3-kinase inhibitor LY294002
    Atsuhiko T Naito
    Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan
    Exp Cell Res 291:56-69. 2003
    ..LY294002 treatment from days 0 to 4 also suppressed Csx/Nkx-2.5 and GATA-4 expression...
  35. ncbi GATA factors lie upstream of Nkx 2.5 in the transcriptional regulatory cascade that effects cardiogenesis
    Alison C Brewer
    Department of Cardiology, King s College Hospital, London SE5 9RS, UK
    Stem Cells Dev 14:425-39. 2005
    ....
  36. pmc Transcription factor Sp3 knockout mice display serious cardiac malformations
    Pieter Fokko Van Loo
    Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands
    Mol Cell Biol 27:8571-82. 2007
    ..Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development and suggest that it has a crucial role in myocardial differentiation...
  37. ncbi Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5
    I Lyons
    Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Australia
    Genes Dev 9:1654-66. 1995
    ..The data demonstrate that Nkx2-5 is essential for normal heart morphogenesis, myogenesis, and function. Furthermore, this gene is a component of a genetic pathway required for myogenic specialization of the ventricles...
  38. ncbi Identification of novel DNA binding targets and regulatory domains of a murine tinman homeodomain factor, nkx-2.5
    C Y Chen
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 270:15628-33. 1995
    ..P. (1993) Development 119, 419-431) was identified as a potential vertebrate homologue of Drosophila tinman, a mesoderm determination factor required for insect heart formation (Bodmer, R. (1993) Development 118, 719-729)...
  39. ncbi Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants
    T J Lints
    Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia
    Development 119:419-31. 1993
    ..Nkx-2.5 expression will therefore be a valuable marker in the analysis of mesoderm development and an early entry point for dissection of the molecular basis of myogenesis in the heart...
  40. ncbi Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants
    T J Lints
    Development 119:969. 1993
  41. pmc Recruitment of the tinman homolog Nkx-2.5 by serum response factor activates cardiac alpha-actin gene transcription
    C Y Chen
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 16:6372-84. 1996
    ..5 homeodomain and to the N-terminal extension of the MADS box. Our study suggests that physical association between Nkx-2.5 and SRF is one way that cardiac specified genes are activated in cardiac cell lineages...
  42. ncbi Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis
    J D Molkentin
    Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center at Dallas, 75235 9148, USA
    Genes Dev 11:1061-72. 1997
    ..We propose that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP...
  43. ncbi Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND
    D Srivastava
    Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235 9148, USA
    Nat Genet 16:154-60. 1997
    ....
  44. ncbi Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development
    C Biben
    The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia
    Genes Dev 11:1357-69. 1997
    ..One aspect of the intrinsic response to L/R information falls under Nkx2-5 homeobox control...
  45. pmc The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression
    Y Lee
    Cardiovascular Research Center, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA
    Mol Cell Biol 18:3120-9. 1998
    ..The cardiac muscle-restricted homeobox protein Csx/Nkx2.5 (Csx) is expressed in the precardiac mesoderm as well as the embryonic and adult heart...
  46. ncbi A GATA-dependent nkx-2.5 regulatory element activates early cardiac gene expression in transgenic mice
    R D Searcy
    Division of Molecular Cardiovascular Biology, The Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
    Development 125:4461-70. 1998
    ..5 in the cardiac, thyroid and spleen primordia...
  47. ncbi Myocyte enhancer factor 2C and Nkx2-5 up-regulate each other's expression and initiate cardiomyogenesis in P19 cells
    I S Skerjanc
    Department of Biochemistry, Medical Sciences Building, University of Western Ontario, London, Ontario N6A 5C1, Canada
    J Biol Chem 273:34904-10. 1998
    ..These findings indicate the presence of a positive regulatory network between Nkx2-5 and MEF2C and show that both factors can direct early stages of cell differentiation into a cardiomyogenic pathway...
  48. ncbi The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development
    M Tanaka
    Cardiovascular Division, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Development 126:1269-80. 1999
    Csx/Nkx2.5 is a vertebrate homeobox gene with a sequence homology to the Drosophila tinman, which is required for the dorsal mesoderm specification...
  49. ncbi Complex modular cis-acting elements regulate expression of the cardiac specifying homeobox gene Csx/Nkx2.5
    M Tanaka
    Cardiovascular Division, and Transgenic Core Facility, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Development 126:1439-50. 1999
    The murine homeobox gene Csx/Nkx2.5 is an evolutionarily highly conserved gene related to the Drosophila tinman gene, which specifies cardiac and visceral mesoderm. Since Csx/Nkx2...
  50. pmc Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis
    M Komada
    Program in Developmental Biology, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genes Dev 13:1475-85. 1999
    ..The vesicular localization of Hrs was disrupted in cells treated with wortmannin, implicating Hrs in the phosphatidylinositol 3-kinase pathway of membrane trafficking...
  51. pmc Phenotypic characterization of the murine Nkx2.6 homeobox gene by gene targeting
    M Tanaka
    Cardiovascular Division, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell Biol 20:2874-9. 2000
    ..Nkx2.6 is a member of the NK-2 homeobox gene family and is most closely related to the Drosophila tinman gene. Nkx2...
  52. ncbi Chamber formation and morphogenesis in the developing mammalian heart
    V M Christoffels
    Department of Anatomy and Embryology, Academic Medical Center, University of Amsterdam, Amsterdam, 1105, The Netherlands
    Dev Biol 223:266-78. 2000
    ....
  53. pmc Nkx2.5 and Nkx2.6, homologs of Drosophila tinman, are required for development of the pharynx
    M Tanaka
    Cardiovascular Division, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell Biol 21:4391-8. 2001
    Nkx2.5 and Nkx2.6 are murine homologs of Drosophila tinman. Their genes are expressed in the ventral region of the pharynx at early stages of embryogenesis...
  54. pmc Progressive atrioventricular conduction defects and heart failure in mice expressing a mutant Csx/Nkx2.5 homeoprotein
    H Kasahara
    Cardiovascular Division, Beth Israel Deaconess Medical Center, and Department of Medicine, Children s Hospital, Boston, Massachusetts, USA
    J Clin Invest 108:189-201. 2001
    ..Recently, ten heterozygous CSX/NKX2.5 homeoprotein mutations were identified in patients with congenital atrioventricular (AV) conduction defects...
  55. pmc Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3
    Vinciane Gaussin
    Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 99:2878-83. 2002
    ..Hence, ALK3 is essential, beyond just the egg cylinder stage, for myocyte-dependent functions and signals in cardiac organogenesis...
  56. pmc Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation
    Petra E M H Habets
    Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Genes Dev 16:1234-46. 2002
    ..5 on the ANF TBE-NKE, and was able to repress ANF promoter activity. Our data provide a potential mechanism for chamber-restricted gene activity in which the cooperative action of Tbx2 and Nkx2.5 inhibits expression in the AVC...
  57. ncbi GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5
    Vidu Garg
    Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Rm NA8 124, Dallas, Texas 75390 9148, USA
    Nature 424:443-7. 2003
    ..These results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5...
  58. ncbi Homeodomain factor Nkx2-5 in heart development and disease
    R P Harvey
    Victor Chang Cardiac Research Institute, Darlinghurst 2010, New South Wales, Australia
    Cold Spring Harb Symp Quant Biol 67:107-14. 2002
  59. ncbi Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart
    Fiona A Stennard
    Victor Chang Cardiac Research Institute, 384 Victoria Street, Darlinghurst, 2010, Sydney, Australia
    Dev Biol 262:206-24. 2003
    ..We propose that Tbx20 plays an integrated role in the ancient myogenic program of the heart, and has been additionally coopted during evolution of vertebrates for endocardial cushion development...
  60. ncbi The cardiac determination factor, Nkx2-5, is activated by mutual cofactors GATA-4 and Smad1/4 via a novel upstream enhancer
    Carl O Brown
    Department of Molecular and Cellular Biology, The Center for Cardiovascular Development, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 279:10659-69. 2004
    The mammalian homologue of Drosophila tinman, Nkx2-5, plays an early role in regulating cardiac genes and morphogenesis...
  61. pmc Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling
    Wei Liu
    Alkek Institute of Biosciences and Technology, Texas A and M University System Health Science Center, 2121 Holcombe Boulevard, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 101:4489-94. 2004
    ..Our findings uncover a previously uncharacterized function for Bmp4 in vascular remodeling of the BAAs, and they show definitively that Bmp4, in cooperation with Bmp7, has a central role in OFT septation...
  62. pmc BMP10 is essential for maintaining cardiac growth during murine cardiogenesis
    Hanying Chen
    Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Development 131:2219-31. 2004
    ..This may provide an underlying mechanism for understanding the pathogenesis of both structural and functional congenital heart defects...
  63. pmc Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system
    Patrick Y Jay
    Department of Cardiology, Children s Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 113:1130-7. 2004
    ..Postnatal conduction defects in Nkx2-5 mutation may result at least in part from a defect in the genetic program that governs the recruitment or retention of embryonic cardiac myocytes in the conduction system...
  64. ncbi Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block
    Mohammad Pashmforoush
    UCSD Institute of Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA
    Cell 117:373-86. 2004
    ..Accordingly, loss of ventricular muscle cell lineage specification into trabecular and conduction system myocytes is a new mechanistic pathway for progressive cardiomyopathy and conduction defects in congenital heart disease...
  65. pmc Targeted inactivation of serum response factor in the developing heart results in myocardial defects and embryonic lethality
    Ara Parlakian
    Laboratoire de Biologie Moléculaire de la Différenciation, Universite Paris 7, 75005 Paris, France
    Mol Cell Biol 24:5281-9. 2004
    ..5, GATA4, myocardin, and the SRF target gene c-fos prior to overt maldevelopment. We conclude that SRF is crucial for cardiac differentiation and maturation, acting as a global regulator of multiple developmental genes...
  66. ncbi Tbx1 has a dual role in the morphogenesis of the cardiac outflow tract
    Huansheng Xu
    Program in Cardiovascular Sciences, Baylor College of Medicine, Houston, TX 77030, USA
    Development 131:3217-27. 2004
    ..Furthermore, our data link, for the first time, the function of the secondary heart field to congenital heart disease...
  67. ncbi GATA4 is a dosage-sensitive regulator of cardiac morphogenesis
    William T Pu
    Department of Cardiology, Children s Hospital Boston, Boston, MA 02115, USA
    Dev Biol 275:235-44. 2004
    ..These data demonstrate that multiple aspects of embryonic cardiac morphogenesis and function are exquisitely sensitive to small changes in GATA4 expression levels...
  68. ncbi CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro
    Ali M Riazi
    Division of Cardiovascular Surgery Research Rm 7017, McMaster Bldg, The Hospital for Sick Children, 555 University Ave, Toronto, M5G 1X8 Ontario, Canada
    J Biol Chem 280:10716-20. 2005
    b>CSX/Nkx2.5 transcription factor plays a pivotal role in cardiac development; however, its role in development and differentiation of other organs has not been investigated...
  69. pmc Morphogenesis of the right ventricle requires myocardial expression of Gata4
    Elisabeth M Zeisberg
    Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 115:1522-31. 2005
    ..Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal...
  70. ncbi Tbx1 expression in pharyngeal epithelia is necessary for pharyngeal arch artery development
    Zhen Zhang
    Department of Pediatrics Cardiology, Baylor College of Medicine, Houston, TX 77030, USA
    Development 132:5307-15. 2005
    ..We also thereby demonstrate conclusively that the role of Tbx1 in fourth PAA development is cell non-autonomous...
  71. ncbi Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18
    Vincent M Christoffels
    Department of Experimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam, The Netherlands
    Circ Res 98:1555-63. 2006
    ....
  72. pmc A threshold of GATA4 and GATA6 expression is required for cardiovascular development
    Mei Xin
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 103:11189-94. 2006
    ....
  73. ncbi Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis
    Christina Karamboulas
    Department of Biochemistry, Medical Sciences Building, University of Western Ontario, London, Ontario, N6A 5C1, Canada
    J Cell Sci 119:4315-21. 2006
    ..Our results show that MEF2C, or genes containing MEF2 DNA-binding sites, is required for the efficient differentiation of cardiomyoblasts into cardiomyocytes, suggesting conservation in the role of MEF2 from Drosophila to mammals...
  74. pmc Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells
    Yunfu Sun
    Skaggs School of Pharmacy, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Dev Biol 304:286-96. 2007
    ..Our studies suggest a role for Isl1 in these distinct domains of expression within the heart...
  75. pmc An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation
    Owen W J Prall
    Victor Chang Cardiac Research Institute, Sydney 2010, Australia
    Cell 128:947-59. 2007
    ....
  76. ncbi Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2
    Yong Zhao
    Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA
    Cell 129:303-17. 2007
    ..These findings indicate that subtle alteration of miRNA dosage can have profound consequences in mammals and demonstrate the utility of mammalian loss-of-function models in revealing physiologic miRNA targets...
  77. pmc Canonical Wnt signaling functions in second heart field to promote right ventricular growth
    Di Ai
    Institute of Biosciences and Technology, Texas A and M System Health Science Center, 2121 Holcombe Boulevard, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 104:9319-24. 2007
    ..Our findings reveal that Wnt signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium...
  78. ncbi A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development
    Ivan P G Moskowitz
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell 129:1365-76. 2007
    ..We conclude that a molecular pathway including Tbx5, Nkx2-5, and Id2 coordinates specification of ventricular myocytes into the ventricular conduction system lineage...
  79. ncbi Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development
    Brian S Snarr
    Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
    Circ Res 101:971-4. 2007
    ..We further demonstrate that abnormal development of the SHF-derived DMP is associated with the pathogenesis of atrioventricular septal defects. These results identify a novel role for the SHF...
  80. doi A myocardial lineage derives from Tbx18 epicardial cells
    Chen Leng Cai
    Skaggs School of Pharmacy, University of California, San Diego, La Jolla, California 92093, USA
    Nature 454:104-8. 2008
    ..The pluripotency of Tbx18 proepicardial cells provides a theoretical framework for applying these progenitors to effect cardiac repair and regeneration...
  81. pmc Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart
    Bin Zhou
    Harvard Stem Cell Institute and Department of Cardiology, Children s Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 454:109-13. 2008
    ..These results identify Wt1(+) epicardial cells as previously unrecognized cardiomyocyte progenitors, and lay the foundation for future efforts to harness the cardiogenic potential of these progenitors for cardiac regeneration and repair...
  82. pmc Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects
    Laura E Briggs
    University of Florida College of Medicine, 1600 SW Archer Rd, M 540, Gainesville, FL 32610 0274, USA
    Circ Res 103:580-90. 2008
    ..These results indicate that Nkx2-5 function is critical not only during cardiac development but also in perinatal hearts, by regulating expression of several important gene products involved in conduction and contraction...
  83. pmc Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium
    Bin Zhou
    Harvard Stem Cell Institute and Department of Cardiology, Children s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA
    Biochem Biophys Res Commun 375:450-3. 2008
    ..Taken together, these results suggest that Nkx2-5 and/or Isl1 cardiac progenitors contribute to proepicardium during heart development...
  84. pmc Reassessment of Isl1 and Nkx2-5 cardiac fate maps using a Gata4-based reporter of Cre activity
    Qing Ma
    Department of Cardiology, Children s Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
    Dev Biol 323:98-104. 2008
    ..These results have important implications for our understanding of cardiac lineage diversification in vivo, and for the interpretation of Cre-based fate maps...
  85. doi Tbx18 and the fate of epicardial progenitors
    Vincent M Christoffels
    Department of Anatomy and Embryology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Meibergdreef 15 L2 108, 1105 AZ Amsterdam, The Netherlands
    Nature 458:E8-9; discussion E9-10. 2009
    ....
  86. pmc Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation
    Morihiko Takeda
    Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32610 0274, USA
    Lab Invest 89:983-93. 2009
    ..These results suggest that Nkx2-5 is necessary for proper conduction and contraction after 2 weeks of age, but with a substantially distinct level of necessity at 2 weeks of age compared with that in the perinatal period...
  87. pmc Six2 activity is required for the formation of the mammalian pyloric sphincter
    Michelle Self
    Department of Genetics and Tumor Cell Biology, MS 331, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105 2794, USA
    Dev Biol 334:409-17. 2009
    ..5, Sox9, and Gremlin) also appear to be required for the formation of this structure in mammals. Thus, we propose that Six2 activity regulates this gene network during the genesis of the pyloric sphincter in the mouse...
  88. doi The sinus venosus progenitors separate and diversify from the first and second heart fields early in development
    Mathilda T M Mommersteeg
    Heart Failure Research Center, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
    Cardiovasc Res 87:92-101. 2010
    ....
  89. pmc Heterogeneity of genetic modifiers ensures normal cardiac development
    Julia B Winston
    Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    Circulation 121:1313-21. 2010
    ..This variability suggests that additional factors can affect or prevent the mutant phenotype. We assess here the role of genetic modifiers and their interactions...
  90. doi Neuregulin 1 sustains the gene regulatory network in both trabecular and nontrabecular myocardium
    Donna Lai
    Victor Chang Cardiac Research Institute, Lowy Packer Building, 405 Liverpool St, Darlinghurst 2010, Australia
    Circ Res 107:715-27. 2010
    ..In development, the membrane-tethered signaling ligand Neuregulin (Nrg)1, expressed in endocardium, is essential for ventricular morphogenesis. In adults, Nrg1 protects against heart failure and can induce cardiomyocytes to divide...
  91. pmc An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation
    Mathieu Nadeau
    Research Unit in Cardiac Growth and Differentiation and Molecular Biology Program, Universite de Montreal, Montreal, QC, Canada H3C 3J7
    Proc Natl Acad Sci U S A 107:19356-61. 2010
    ....
  92. doi Loss of Cited2 causes congenital heart disease by perturbing left-right patterning of the body axis
    Kylie Lopes Floro
    Developmental Biology Division, Victor Chang Cardiac Research Institute, Sydney, Australia
    Hum Mol Genet 20:1097-110. 2011
    ..The clinical relevance of these findings lies in the fact that heterozygous mutation of human CITED2 is associated with congenital heart disease and laterality defects...
  93. pmc Nkx2-5 represses Gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis
    Arianna Caprioli
    Center for Developmental Biology, University of Texas Southwestern Medical Center, Dallas, USA
    Circulation 123:1633-41. 2011
    ..Studies also suggest that specification of these lineages is inversely regulated. However, the transcriptional networks that govern the cell fate specification of these progenitors are incompletely defined...
  94. pmc Expression of sumoylation deficient Nkx2.5 mutant in Nkx2.5 haploinsufficient mice leads to congenital heart defects
    Eun Young Kim
    Program in Genes and Development, University of Texas Health Science Center at Houston, Houston, Texas, United States of America
    PLoS ONE 6:e20803. 2011
    Nkx2.5 is a cardiac specific homeobox gene critical for normal heart development. We previously identified Nkx2.5 as a target of sumoylation, a posttranslational modification implicated in a variety of cellular activities...
  95. doi GATA5 interacts with GATA4 and GATA6 in outflow tract development
    Brigitte Laforest
    Laboratoire de développement et différentiation cardiaque, Programme de biologie moléculaire, Universite de Montreal, Montreal QC, Canada H3C 3J7
    Dev Biol 358:368-78. 2011
    ..The data identify GATA5 as a potential genetic modifier of congenital heart disease and provide insight for elucidating the genetic basis of an important class of human birth defects...
  96. pmc The heart endocardium is derived from vascular endothelial progenitors
    Michal Milgrom-Hoffman
    Department of Biological Regulation, Weizmann Institute of Science, 76100 Rehovot, Israel
    Development 138:4777-87. 2011
    ..Collectively, our findings demonstrate that the second heart field contains distinct myocardial and endocardial progenitor populations. We suggest that the endocardium derives, at least in part, from vascular endothelial cells...
  97. doi Wt1 and epicardial fate mapping
    Carsten Rudat
    Institut fur Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany
    Circ Res 111:165-9. 2012
    ..Genetic lineage tracing systems based on Wt1 regulatory sequences provided evidence that epicardium-derived cells also adopt a myocardial fate in the mouse...
  98. pmc Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation
    Serge Gregoire
    Department of Medicine, Division of Cardiology, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA
    Circ Res 112:900-10. 2013
    ..Cardiogenesis is regulated by a complex interplay between transcription factors. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs)...
  99. pmc Csx: a murine homeobox-containing gene specifically expressed in the developing heart
    I Komuro
    Molecular Medicine Divisions, Beth Israel Hospital, Boston, MA 02215
    Proc Natl Acad Sci U S A 90:8145-9. 1993
    ..We report here on the cloning of a murine homeobox cDNA, Csx (cardiac-specific homeobox)...
  100. ncbi An HF-1a/HF-1b/MEF-2 combinatorial element confers cardiac ventricular specificity and established an anterior-posterior gradient of expression
    R S Ross
    Department of Medicine, Center for Molecular Genetics, University of California, San Diego, School of Medicine, La Jolla 92093, USA
    Development 122:1799-809. 1996
    ..The patterned expression of this transgene may provide a model system in which to investigate the cues that dictate anterior-posterior (right ventricle/left ventricle) gradients during mammalian heart development...
  101. ncbi Embryonic expression of an Nkx2-5/Cre gene using ROSA26 reporter mice
    K A Moses
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Genesis 31:176-80. 2001
    ..The Nkx2-5/Cre mouse model should provide a useful genetic resource to elucidate the role of loxP manipulated genetic targets in cardiogenesis and other developmental processes...

Research Grants9

  1. SMAD MEDIATED SIGNALING DURING LUNG MORPHOGENESIS
    Wei Shi; Fiscal Year: 2002
    ..The results of this project will provide new rationales for novel therapeutic strategies to modulate TGF-beta signaling during lung development, injury, repair, and disease. ..
  2. PHOSPHOLIPASE C AND CARDIAC HYPERTROPHY
    GERALD DORN; Fiscal Year: 2005
    ..abstract_text> ..
  3. Calpains as Mediators of Cardiac Ischemic Injury
    Gerald W Dorn; Fiscal Year: 2010
    ..Collectively, these studies will apply state-of-the-art techniques for in vivo genetic manipulation, microphysiologic analysis, and biochemical assessment to achieve insight into the roles of myocardial calpains in health and disease. ..
  4. HAND GENES IN CARDIAC DEVELOPMENT
    William Pu; Fiscal Year: 2004
    ..This experience, and the information generated in this plan, will launch the applicant's career as an independent investigator. ..
  5. THE ROLE OF UFD1 AND CDC45 IN NEURAL CREST DEVELOPMENT
    Vidu Garg; Fiscal Year: 2004
    ..The function of Cdc45 will be examined in vivo in chick embryos by retrovirally mediated alteration of gene expression. A yeast two hybrid assay will be utilized to determine if Ufdl, Cdc45, and Hira interact with one another. ..
  6. Regulation of Key Processes in Oocyte Biology
    Martin Matzuk; Fiscal Year: 2007
    ..Compromised fertility in knockout models lacking these oocyte-specific genes would demonstrate that these proteins are potential contraceptive targets and possibly mutated in infertile women. ..
  7. Fetal Lung Development:Role of Wnt5a Signaling
    Changgong Li; Fiscal Year: 2008
    ..This information will be of utility in understanding the molecular mechanisms of congenital and induced lung disease. ..
  8. Defining the Mammalian Intercellular Bridge Interactome
    Martin M Matzuk; Fiscal Year: 2010
    ..Our proposed Specific Aims will also help us to develop additional high throughput screening assays for the identification of small molecule disruptors of the intercellular bridge. ..
  9. MOUSE MODELS TO STUDY GONADAL TUMOR DEVELOPMENT
    Martin M Matzuk; Fiscal Year: 2010
    ..Characterization of these mice will lead to important insights into the development of gonadal cancers in men and women and the roles of several proteins in reproductive physiology. ..