Results Distinct and Overlapping Expression Patterns of Dll 4 , Jag 1 , and Notch 1 Intracellular

Congenital heart defects (CHDs) are the most common structural anomalies, affecting 0.8% of live births worldwide. Heart valve malformations, occurring either in isolation or in the context of syndromic disease, account for about one third of all CHDs. However, these estimates do not take into account the bicuspid aortic valve (BAV), which is present in ≈0.5% to 2% of the population. A BAV predisposes to valve calcification and stenosis, and complications in 30% of BAV patients result in more morbidity and mortality than all other CHD combined. Patients with aortic valve (AV) disease at any age manifest some type of structural malformation frequently in association with aortic coarctation or aneurysm, suggesting a common underlying developmental mechanism affecting the entire aortic root and thoracic aorta. Valve formation, best characterized in the mouse, begins with an epithelial–mesenchymal transition (EMT), whereby endocardial cells in the mouse E9.5 atrioventricular canal (AVC) and E10.5 outflow tract (OFT) detach from each other to yield mesenchyme Cellular Biology

[1]  Akiyoshi Uemura,et al.  Sequential Notch activation regulates ventricular chamber development , 2015, Nature Cell Biology.

[2]  Emily J. Farrar,et al.  Notch-Tnf signalling is required for development and homeostasis of arterial valves , 2015, European heart journal.

[3]  M. Ricote,et al.  GOplot: an R package for visually combining expression data with functional analysis , 2015, Bioinform..

[4]  L. Leinwand,et al.  Spontaneous Aortic Regurgitation and Valvular Cardiomyopathy in Mice , 2015, Arteriosclerosis, thrombosis, and vascular biology.

[5]  N. Perrimon,et al.  Mechanical Allostery: Evidence for a Force Requirement in the Proteolytic Activation of Notch. , 2015, Developmental cell.

[6]  P. Scambler,et al.  The CXCL12/CXCR4 Axis Plays a Critical Role in Coronary Artery Development , 2015, Developmental cell.

[7]  Janan T. Eppig,et al.  Global genetic analysis in mice unveils central role for cilia in congenital heart disease , 2015, Nature.

[8]  J. Aviérinos,et al.  Loss of Krox20 results in aortic valve regurgitation and impaired transcriptional activation of fibrillar collagen genes. , 2014, Cardiovascular research.

[9]  M. Chu,et al.  Bicuspid aortic valve disease , 2013, Canadian Medical Association Journal.

[10]  H. Stunnenberg,et al.  Dynamic binding of RBPJ is determined by Notch signaling status. , 2013, Genes & development.

[11]  V. Taylor,et al.  Endocardial to Myocardial Notch-Wnt-Bmp Axis Regulates Early Heart Valve Development , 2013, PloS one.

[12]  Carlos Torroja,et al.  Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy , 2013, Nature Medicine.

[13]  Freddy Radtke,et al.  Endothelial deletion of murine Jag1 leads to valve calcification and congenital heart defects associated with Alagille syndrome , 2012, Development.

[14]  Bin Zhou,et al.  Partitioning the heart: mechanisms of cardiac septation and valve development , 2012, Development.

[15]  R. Hinton.  Bicuspid Aortic Valve and Thoracic Aortic Aneurysm: Three Patient Populations, Two Disease Phenotypes, and One Shared Genotype , 2012, Cardiology research and practice.

[16]  N. Spinner,et al.  Notch signaling in human development and disease. , 2012, Seminars in cell & developmental biology.

[17]  J. Roos‐Hesselink,et al.  Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. , 2011, Journal of the American College of Cardiology.

[18]  J. Redondo,et al.  Regulator of calcineurin 1 mediates pathological vascular wall remodeling , 2011, The Journal of experimental medicine.

[19]  Colin N. Dewey,et al.  RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome , 2011, BMC Bioinformatics.

[20]  Matko Bosnjak,et al.  REVIGO Summarizes and Visualizes Long Lists of Gene Ontology Terms , 2011, PloS one.

[21]  Bin Zhou,et al.  Nfatc1 Coordinates Valve Endocardial Cell Lineage Development Required for Heart Valve Formation , 2011, Circulation research.

[22]  G. Andelfinger,et al.  Loss of Gata5 in mice leads to bicuspid aortic valve. , 2011, The Journal of clinical investigation.

[23]  Marcel Martin.  Cutadapt removes adapter sequences from high-throughput sequencing reads , 2011 .

[24]  R. Hinton,et al.  Heart valve structure and function in development and disease. , 2011, Annual review of physiology.

[25]  J. Epstein,et al.  Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves. , 2011, The Journal of clinical investigation.

[26]  J. Redondo,et al.  Alternative promoter usage at the Notch1 locus supports ligand-independent signaling in T cell development and leukemogenesis. , 2010, Immunity.

[27]  S. Blacklow,et al.  Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes , 2010, Nature Structural &Molecular Biology.

[28]  E. Mekada,et al.  HB-EGF function in cardiac valve development requires interaction with heparan sulfate proteoglycans , 2010, Development.

[29]  A. Barberis,et al.  Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis , 2010, Nature.

[30]  J. Griffin,et al.  Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion , 2009, British Journal of Cancer.

[31]  A. C. Durán,et al.  Bicuspid aortic valves with different spatial orientations of the leaflets are distinct etiological entities. , 2009, Journal of the American College of Cardiology.

[32]  D. Srivastava,et al.  Notch1 represses osteogenic pathways in aortic valve cells. , 2009, Journal of molecular and cellular cardiology.

[33]  Davis J. McCarthy,et al.  edgeR: a Bioconductor package for differential expression analysis of digital gene expression data , 2009, Bioinform..

[34]  K. Yutzey,et al.  Heart Valve Development: Regulatory Networks in Development and Disease , 2009, Circulation research.

[35]  K. Kaestner,et al.  Murine Jagged1/Notch signaling in the second heart field orchestrates Fgf8 expression and tissue-tissue interactions during outflow tract development. , 2009, The Journal of clinical investigation.

[36]  Raphael Kopan,et al.  The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism , 2009, Cell.

[37]  T. Tadros,et al.  Ascending aortic dilatation associated with bicuspid aortic valve: pathophysiology, molecular biology, and clinical implications. , 2009, Circulation.

[38]  N. Manley,et al.  Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment , 2008, The Journal of experimental medicine.

[39]  A. Wessels,et al.  Origin and fate of cardiac mesenchyme , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[40]  R. Markwald,et al.  Periostin regulates atrioventricular valve maturation. , 2008, Developmental biology.

[41]  Y. Jan,et al.  An Obligatory Role of Mind Bomb-1 in Notch Signaling of Mammalian Development , 2007, PloS one.

[42]  Richard P. Harvey,et al.  Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7 , 2007, Proceedings of the National Academy of Sciences.

[43]  Victoria Bolós,et al.  Monitoring Notch1 activity in development: Evidence for a feedback regulatory loop , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[44]  C. Steidl,et al.  Combined Loss of Hey1 and HeyL Causes Congenital Heart Defects Because of Impaired Epithelial to Mesenchymal Transition , 2007, Circulation research.

[45]  J. Ruijter,et al.  Three‐dimensional measurement and visualization of morphogenesis applied to cardiac embryology , 2007, Journal of microscopy.

[46]  E. Ballestar,et al.  Notch signaling is essential for ventricular chamber development. , 2007, Developmental cell.

[47]  Piotr Sliz,et al.  Cooperative assembly of higher-order Notch complexes functions as a switch to induce transcription , 2007, Proceedings of the National Academy of Sciences.

[48]  J. Klingensmith,et al.  The Bone Morphogenetic Protein Antagonist Noggin Regulates Mammalian Cardiac Morphogenesis , 2007, Circulation research.

[49]  R. Hinton,et al.  Extracellular Matrix Remodeling and Organization in Developing and Diseased Aortic Valves , 2006, Circulation research.

[50]  R. Schwartz,et al.  Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning , 2005, Development.

[51]  K. Sangkuhl,et al.  Identification of Receptors and Signaling Pathways for Orphan Bone Morphogenetic Protein/Growth Differentiation Factor Ligands Based on Genomic Analyses* , 2005, Journal of Biological Chemistry.

[52]  D. Srivastava,et al.  Mutations in NOTCH1 cause aortic valve disease , 2005, Nature.

[53]  U. Suter,et al.  Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation. , 2005, Blood.

[54]  Tasuku Honjo,et al.  Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants. , 2004, Genes & development.

[55]  Janet Rossant,et al.  Dosage-sensitive requirement for mouse Dll4 in artery development. , 2004, Genes & development.

[56]  E. Délot,et al.  Control of endocardial cushion and cardiac valve maturation by BMP signaling pathways. , 2003, Molecular genetics and metabolism.

[57]  David C. Lee,et al.  Form and function of developing heart valves: coordination by extracellular matrix and growth factor signaling , 2003, Journal of Molecular Medicine.

[58]  David C. Lee,et al.  Defective valvulogenesis in HB‐EGF and TACE‐null mice is associated with aberrant BMP signaling , 2003, The EMBO journal.

[59]  Masatsugu Hori,et al.  Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Bruce D Gelb,et al.  PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. , 2002, American journal of human genetics.

[61]  S. Gerety,et al.  Cardiovascular ephrinB2 function is essential for embryonic angiogenesis. , 2002, Development.

[62]  R. Kim,et al.  Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. , 2001, Developmental biology.

[63]  R. Hammer,et al.  Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo. , 2001, Developmental biology.

[64]  M. Gimbrone,et al.  A role for Smad6 in development and homeostasis of the cardiovascular system , 2000, Nature Genetics.

[65]  N. Spinner,et al.  The expression of Jagged1 in the developing mammalian heart correlates with cardiovascular disease in Alagille syndrome. , 1999, Human molecular genetics.

[66]  H. Macdonald,et al.  Deficient T cell fate specification in mice with an induced inactivation of Notch1. , 1999, Immunity.

[67]  S. Artavanis-Tsakonas,et al.  Notch signaling: cell fate control and signal integration in development. , 1999, Science.

[68]  M. Mallo,et al.  Hoxa-2 restricts the chondrogenic domain and inhibits bone formation during development of the branchial area. , 1998, Development.

[69]  J. Massagué,et al.  Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. , 1998, Genes & development.

[70]  M. Kretzschmar,et al.  Opposing BMP and EGF signalling pathways converge on the TGF-β family mediator Smad1 , 1997, Nature.

[71]  Paul S. Meltzer,et al.  Mutations in the human Jagged1 gene are responsible for Alagille syndrome , 1997, Nature Genetics.

[72]  Colin C. Collins,et al.  Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1 , 1997, Nature Genetics.

[73]  K. Irvine,et al.  Fringe modulates Notch–ligand interactions , 1997, Nature.

[74]  J. Posakony,et al.  Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity. , 1995, Genes & development.

[75]  T. Mak,et al.  Disruption of the mouse RBP-J kappa gene results in early embryonic death. , 1995, Development.

[76]  R R Markwald,et al.  Molecular regulation of atrioventricular valvuloseptal morphogenesis. , 1995, Circulation research.

[77]  BMC Bioinformatics BioMed Central , 2008 .

[78]  Cheng Li,et al.  Adjusting batch effects in microarray expression data using empirical Bayes methods. , 2007, Biostatistics.

[79]  Frank McCormick,et al.  Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. , 2004, Genes & development.

[80]  Cheol‐Hee Kim,et al.  Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. , 2003, Developmental cell.

[81]  E. Stanley,et al.  Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3'UTR-ires-Cre allele of the homeobox gene Nkx2-5. , 2002, The International journal of developmental biology.

[82]  Raymond B. Runyan,et al.  Invasion of mesenchyme into three-dimensional collagen gels: a regional and temporal analysis of interaction in embryonic heart tissue. , 1983, Developmental biology.