 Benoit Bruneau, PhD
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| Title | Professor in Residence |
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| School | UCSF School of Medicine |
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| Department | Pediatrics |
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| Address | Gladstone - 1650 Owens Street
San Francisco CA 94158
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| Phone | 415-734-2708 |
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 Overview The main focus of our lab is to understand how a heart becomes a heart: what cell lineage decisions take place to direct cardiac differentiation, and what morphogenetic and patterning processes occur to assemble all of the heart's components into a functional organ. We are primarily interested in regulation of these processes by transcriptional regulatory mechanisms that include DNA-binding transcription factors, chromatin remodeling complexes, and histone modifications. We have used this knowledge to understand disease mechanisms, but also to devise strategies for cardiac regeneration.
Why study heart development? We believe that primary defects in patterning in early heart development are at the root of congenital heart defects, which affect approximately 1% of live-born children, and we want to understand how these defects occur, to perhaps be able to uncover new and improved diagnostic or even therapeutic options. Also, by understanding how cardiac lineage specification occurs, we can better design stem cell-based interventions of cardiac repair, based on the knowledge of what drives an uncommitted cell towards a specific cardiac fate. We have recently focused our efforts on cardiac chromatin remodeling and modification factors, enzymes that unwind DNA or modify histones to turn genes on or off. We are particularly interested in how these factors control cardiac cell lineage decisions. These chromatin remodeling factors may also be key to pushing a stem cell into becoming a heart cell, perhaps opening up new avenues for cardiac regenerative medicine.
Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications.
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Bruneau BG. Signaling and transcriptional networks in heart development and regeneration. Cold Spring Harb Perspect Biol. 2013; 5(3).
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Star EN, Zhu M, Shi Z, Liu H, Pashmforoush M, Sauve Y, Bruneau BG, Chow RL. Regulation of retinal interneuron subtype identity by the Iroquois homeobox gene Irx6. Development. 2012 Dec; 139(24):4644-55.
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Gaborit N, Sakuma R, Wylie JN, Kim KH, Zhang SS, Hui CC, Bruneau BG. Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology. Development. 2012 Nov; 139(21):4007-19.
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Wamstad JA, Alexander JM, Truty RM, Shrikumar A, Li F, Eilertson KE, Ding H, Wylie JN, Pico AR, Capra JA, Erwin G, Kattman SJ, Keller GM, Srivastava D, Levine SS, Pollard KS, Holloway AK, Boyer LA, Bruneau BG. Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage. Cell. 2012 Sep 28; 151(1):206-20.
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Kim KH, Rosen A, Bruneau BG, Hui CC, Backx PH. Iroquois homeodomain transcription factors in heart development and function. Circ Res. 2012 May 25; 110(11):1513-24.
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Delgado-Olguín P, Huang Y, Li X, Christodoulou D, Seidman CE, Seidman JG, Tarakhovsky A, Bruneau BG. Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis. Nat Genet. 2012 Mar; 44(3):343-7.
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Chang CP, Bruneau BG. Epigenetics and cardiovascular development. Annu Rev Physiol. 2012; 74:41-68.
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Zhang SS, Kim KH, Rosen A, Smyth JW, Sakuma R, Delgado-Olguín P, Davis M, Chi NC, Puviindran V, Gaborit N, Sukonnik T, Wylie JN, Brand-Arzamendi K, Farman GP, Kim J, Rose RA, Marsden PA, Zhu Y, Zhou YQ, Miquerol L, Henkelman RM, Stainier DY, Shaw RM, Hui CC, Bruneau BG, Backx PH. Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network. Proc Natl Acad Sci U S A. 2011 Aug 16; 108(33):13576-81.
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Bruneau BG. Atrial natriuretic factor in the developing heart: a signpost for cardiac morphogenesis. Can J Physiol Pharmacol. 2011 Aug; 89(8):533-7.
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Wyngaarden LA, Delgado-Olguin P, Su IH, Bruneau BG, Hopyan S. Ezh2 regulates anteroposterior axis specification and proximodistal axis elongation in the developing limb. Development. 2011 Sep; 138(17):3759-67.
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Qian L, Wythe JD, Liu J, Cartry J, Vogler G, Mohapatra B, Otway RT, Huang Y, King IN, Maillet M, Zheng Y, Crawley T, Taghli-Lamallem O, Semsarian C, Dunwoodie S, Winlaw D, Harvey RP, Fatkin D, Towbin JA, Molkentin JD, Srivastava D, Ocorr K, Bruneau BG, Bodmer R. Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species. J Cell Biol. 2011 Jun 27; 193(7):1181-96.
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Fish JE, Wythe JD, Xiao T, Bruneau BG, Stainier DY, Srivastava D, Woo S. A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish. Development. 2011 Apr; 138(7):1409-19.
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Takeuchi JK, Lou X, Alexander JM, Sugizaki H, Delgado-Olguín P, Holloway AK, Mori AD, Wylie JN, Munson C, Zhu Y, Zhou YQ, Yeh RF, Henkelman RM, Harvey RP, Metzger D, Chambon P, Stainier DY, Pollard KS, Scott IC, Bruneau BG. Chromatin remodelling complex dosage modulates transcription factor function in heart development. Nat Commun. 2011; 2:187.
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Delgado-Olguín P, Brand-Arzamendi K, Scott IC, Jungblut B, Stainier DY, Bruneau BG, Recillas-Targa F. CTCF promotes muscle differentiation by modulating the activity of myogenic regulatory factors. J Biol Chem. 2011 Apr 8; 286(14):12483-94.
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Nadeau M, Georges RO, Laforest B, Yamak A, Lefebvre C, Beauregard J, Paradis P, Bruneau BG, Andelfinger G, Nemer M. An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation. Proc Natl Acad Sci U S A. 2010 Nov 9; 107(45):19356-61.
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Puskaric S, Schmitteckert S, Mori AD, Glaser A, Schneider KU, Bruneau BG, Blaschke RJ, Steinbeisser H, Rappold G. Shox2 mediates Tbx5 activity by regulating Bmp4 in the pacemaker region of the developing heart. Hum Mol Genet. 2010 Dec 1; 19(23):4625-33.
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Bruneau BG. Chromatin remodeling in heart development. Curr Opin Genet Dev. 2010 Oct; 20(5):505-11.
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Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 2010 Aug 6; 142(3):375-86.
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Bruneau BG. Epigenetic regulation of the cardiovascular system: introduction to a review series. Circ Res. 2010 Aug 6; 107(3):324-6.
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Alexander JM, Bruneau BG. Lessons for cardiac regeneration and repair through development. Trends Mol Med. 2010 Sep; 16(9):426-34.
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Kuo YM, Li Z, Jiao Y, Gaborit N, Pani AK, Orrison BM, Bruneau BG, Giasson BI, Smeyne RJ, Gershon MD, Nussbaum RL. Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated alpha-synuclein gene mutations precede central nervous system changes. Hum Mol Genet. 2010 May 1; 19(9):1633-50.
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Fouladkou F, Lu C, Jiang C, Zhou L, She Y, Walls JR, Kawabe H, Brose N, Henkelman RM, Huang A, Bruneau BG, Rotin D. The ubiquitin ligase Nedd4-1 is required for heart development and is a suppressor of thrombospondin-1. J Biol Chem. 2010 Feb 26; 285(9):6770-80.
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Koshiba-Takeuchi K, Mori AD, Kaynak BL, Cebra-Thomas J, Sukonnik T, Georges RO, Latham S, Beck L, Beck L, Henkelman RM, Black BL, Olson EN, Wade J, Takeuchi JK, Nemer M, Gilbert SF, Bruneau BG. Reptilian heart development and the molecular basis of cardiac chamber evolution. Nature. 2009 Sep 3; 461(7260):95-8.
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Riazi AM, Takeuchi JK, Hornberger LK, Zaidi SH, Amini F, Coles J, Bruneau BG, Van Arsdell GS. NKX2-5 regulates the expression of beta-catenin and GATA4 in ventricular myocytes. PLoS One. 2009; 4(5):e5698.
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Takeuchi JK, Bruneau BG. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature. 2009 Jun 4; 459(7247):708-11.
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Ellis J, Bruneau BG, Keller G, Lemischka IR, Nagy A, Rossant J, Srivastava D, Zandstra PW, Stanford WL. Alternative induced pluripotent stem cell characterization criteria for in vitro applications. Cell Stem Cell. 2009 Mar 6; 4(3):198-9; author reply 202.
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Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008 Aug; 15(2):272-84.
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Zhu Y, Gramolini AO, Walsh MA, Zhou YQ, Slorach C, Friedberg MK, Takeuchi JK, Sun H, Henkelman RM, Backx PH, Redington AN, Maclennan DH, Bruneau BG. Tbx5-dependent pathway regulating diastolic function in congenital heart disease. Proc Natl Acad Sci U S A. 2008 Apr 8; 105(14):5519-24.
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Bruneau BG. The developmental genetics of congenital heart disease. Nature. 2008 Feb 21; 451(7181):943-8.
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Feintuch A, Zhu Y, Bishop J, Davidson L, Dazai J, Bruneau BG, Henkelman RM. 4D cardiac MRI in the mouse. NMR Biomed. 2007 May; 20(3):360-5.
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Bruneau BG, Black BL. The heart's Da Vinci code: a Renaissance at Keystone. Development. 2007 May; 134(9):1631-3.
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Takeuchi JK, Lickert H, Bisgrove BW, Sun X, Yamamoto M, Chawengsaksophak K, Hamada H, Yost HJ, Rossant J, Bruneau BG. Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry. Proc Natl Acad Sci U S A. 2007 Jan 16; 104(3):846-51.
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Takeuchi JK, Bruneau BG. Irxl1, a divergent Iroquois homeobox family transcription factor gene. Gene Expr Patterns. 2007 Jan; 7(1-2):51-6.
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Mori AD, Zhu Y, Vahora I, Nieman B, Koshiba-Takeuchi K, Davidson L, Pizard A, Seidman JG, Seidman CE, Chen XJ, Henkelman RM, Bruneau BG. Tbx5-dependent rheostatic control of cardiac gene expression and morphogenesis. Dev Biol. 2006 Sep 15; 297(2):566-86.
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Delgado-Olguín P, Takeuchi JK, Bruneau BG. Chromatin modification and remodeling in heart development. ScientificWorldJournal. 2006; 6:1851-61.
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Bruneau BG. [Irx5: a transcription factor that regulates the cardiac repolarization gradient]. Med Sci (Paris). 2006 Mar; 22(3):231-2.
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Koshiba-Takeuchi K, Takeuchi JK, Arruda EP, Kathiriya IS, Mo R, Hui CC, Srivastava D, Bruneau BG. Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nat Genet. 2006 Feb; 38(2):175-83.
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Costantini DL, Arruda EP, Agarwal P, Kim KH, Zhu Y, Zhu W, Lebel M, Cheng CW, Park CY, Pierce SA, Guerchicoff A, Pollevick GD, Chan TY, Kabir MG, Cheng SH, Husain M, Antzelevitch C, Srivastava D, Gross GJ, Hui CC, Backx PH, Bruneau BG. The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Cell. 2005 Oct 21; 123(2):347-58.
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Flenniken AM, Osborne LR, Anderson N, Ciliberti N, Fleming C, Gittens JE, Gong XQ, Kelsey LB, Lounsbury C, Moreno L, Nieman BJ, Peterson K, Qu D, Roscoe W, Shao Q, Tong D, Veitch GI, Voronina I, Vukobradovic I, Wood GA, Zhu Y, Zirngibl RA, Aubin JE, Bai D, Bruneau BG, Grynpas M, Henderson JE, Henkelman RM, McKerlie C, Sled JG, Stanford WL, Laird DW, Kidder GM, Adamson SL, Rossant J. A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia. Development. 2005 Oct; 132(19):4375-86.
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Cheng CW, Chow RL, Lebel M, Sakuma R, Cheung HO, Thanabalasingham V, Zhang X, Bruneau BG, Birch DG, Hui CC, McInnes RR, Cheng SH. The Iroquois homeobox gene, Irx5, is required for retinal cone bipolar cell development. Dev Biol. 2005 Nov 1; 287(1):48-60.
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Frey BJ, Mohammad N, Morris QD, Zhang W, Robinson MD, Mnaimneh S, Chang R, Pan Q, Sat E, Rossant J, Bruneau BG, Aubin JE, Blencowe BJ, Hughes TR. Genome-wide analysis of mouse transcripts using exon microarrays and factor graphs. Nat Genet. 2005 Sep; 37(9):991-6.
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Bruneau BG. Developmental biology: tiny brakes for a growing heart. Nature. 2005 Jul 14; 436(7048):181-2.
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Pizard A, Burgon PG, Paul DL, Bruneau BG, Seidman CE, Seidman JG. Connexin 40, a target of transcription factor Tbx5, patterns wrist, digits, and sternum. Mol Cell Biol. 2005 Jun; 25(12):5073-83.
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Zhou YQ, Zhu Y, Bishop J, Davidson L, Henkelman RM, Bruneau BG, Foster FS. Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome. Am J Physiol Heart Circ Physiol. 2005 Sep; 289(3):H992-H1001.
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Takeuchi JK, Mileikovskaia M, Koshiba-Takeuchi K, Heidt AB, Mori AD, Arruda EP, Gertsenstein M, Georges R, Davidson L, Mo R, Hui CC, Henkelman RM, Nemer M, Black BL, Nagy A, Bruneau BG. Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development. Development. 2005 May; 132(10):2463-74.
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Barron MR, Belaguli NS, Zhang SX, Trinh M, Iyer D, Merlo X, Lough JW, Parmacek MS, Bruneau BG, Schwartz RJ. Serum response factor, an enriched cardiac mesoderm obligatory factor, is a downstream gene target for Tbx genes. J Biol Chem. 2005 Mar 25; 280(12):11816-28.
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Zhang W, Morris QD, Chang R, Shai O, Bakowski MA, Mitsakakis N, Mohammad N, Robinson MD, Zirngibl R, Somogyi E, Laurin N, Eftekharpour E, Sat E, Grigull J, Pan Q, Peng WT, Krogan N, Greenblatt J, Fehlings M, van der Kooy D, Aubin J, Bruneau BG, Rossant J, Blencowe BJ, Frey BJ, Hughes TR. The functional landscape of mouse gene expression. J Biol. 2004; 3(5):21.
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Lickert H, Takeuchi JK, Von Both I, Walls JR, McAuliffe F, Adamson SL, Henkelman RM, Wrana JL, Rossant J, Bruneau BG. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature. 2004 Nov 4; 432(7013):107-12.
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McPherson JP, Tamblyn L, Elia A, Migon E, Shehabeldin A, Matysiak-Zablocki E, Lemmers B, Salmena L, Hakem A, Fish J, Kassam F, Squire J, Bruneau BG, Hande MP, Hakem R. Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. EMBO J. 2004 Sep 15; 23(18):3677-88.
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Moskowitz IP, Pizard A, Patel VV, Bruneau BG, Kim JB, Kupershmidt S, Roden D, Berul CI, Seidman CE, Seidman JG. The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system. Development. 2004 Aug; 131(16):4107-16.
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Xu H, Morishima M, Wylie JN, Schwartz RJ, Bruneau BG, Lindsay EA, Baldini A. Tbx1 has a dual role in the morphogenesis of the cardiac outflow tract. Development. 2004 Jul; 131(13):3217-27.
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Mori AD, Bruneau BG. TBX5 mutations and congenital heart disease: Holt-Oram syndrome revealed. Curr Opin Cardiol. 2004 May; 19(3):211-5.
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Lebel M, Agarwal P, Cheng CW, Kabir MG, Chan TY, Thanabalasingham V, Zhang X, Cohen DR, Husain M, Cheng SH, Bruneau BG, Hui CC. The Iroquois homeobox gene Irx2 is not essential for normal development of the heart and midbrain-hindbrain boundary in mice. Mol Cell Biol. 2003 Nov; 23(22):8216-25.
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Stennard FA, Costa MW, Elliott DA, Rankin S, Haast SJ, Lai D, McDonald LP, Niederreither K, Dolle P, Bruneau BG, Zorn AM, Harvey RP. Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Dev Biol. 2003 Oct 15; 262(2):206-24.
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Rallis C, Bruneau BG, Del Buono J, Seidman CE, Seidman JG, Nissim S, Tabin CJ, Logan MP. Tbx5 is required for forelimb bud formation and continued outgrowth. Development. 2003 Jun; 130(12):2741-51.
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Bruneau BG. The developing heart and congenital heart defects: a make or break situation. Clin Genet. 2003 Apr; 63(4):252-61.
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Agarwal P, Wylie JN, Galceran J, Arkhitko O, Li C, Deng C, Grosschedl R, Bruneau BG. Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo. Development. 2003 Feb; 130(3):623-33.
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Bruneau BG. Transcriptional regulation of vertebrate cardiac morphogenesis. Circ Res. 2002 Mar 22; 90(5):509-19.
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Bruneau BG, Nemer G, Schmitt JP, Charron F, Robitaille L, Caron S, Conner DA, Gessler M, Nemer M, Seidman CE, Seidman JG. A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell. 2001 Sep 21; 106(6):709-21.
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Bruneau BG, Bao ZZ, Fatkin D, Xavier-Neto J, Georgakopoulos D, Maguire CT, Berul CI, Kass DA, Kuroski-de Bold ML, de Bold AJ, Conner DA, Rosenthal N, Cepko CL, Seidman CE, Seidman JG. Cardiomyopathy in Irx4-deficient mice is preceded by abnormal ventricular gene expression. Mol Cell Biol. 2001 Mar; 21(5):1730-6.
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Bruneau BG, Bao ZZ, Tanaka M, Schott JJ, Izumo S, Cepko CL, Seidman JG, Seidman CE. Cardiac expression of the ventricle-specific homeobox gene Irx4 is modulated by Nkx2-5 and dHand. Dev Biol. 2000 Jan 15; 217(2):266-77.
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Bruneau BG, Logan M, Davis N, Levi T, Tabin CJ, Seidman JG, Seidman CE. Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome. Dev Biol. 1999 Jul 1; 211(1):100-8.
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Ogawa T, Vatta M, Bruneau BG, de Bold AJ. Characterization of natriuretic peptide production by adult heart atria. Am J Physiol. 1999 Jun; 276(6 Pt 2):H1977-86.
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Bao ZZ, Bruneau BG, Seidman JG, Seidman CE, Cepko CL. Regulation of chamber-specific gene expression in the developing heart by Irx4. Science. 1999 Feb 19; 283(5405):1161-4.
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Ogawa T, Bruneau BG, Yokota N, de Bold ML, de Bold AJ. Tissue-specific regulation of renal and cardiac atrial natriuretic factor gene expression in deoxycorticosterone acetate-salt rats. Hypertension. 1997 Dec; 30(6):1342-7.
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Bruneau BG, Piazza LA, de Bold AJ. BNP gene expression is specifically modulated by stretch and ET-1 in a new model of isolated rat atria. Am J Physiol. 1997 Dec; 273(6 Pt 2):H2678-86.
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Bamshad M, Lin RC, Law DJ, Watkins WC, Krakowiak PA, Moore ME, Franceschini P, Lala R, Holmes LB, Gebuhr TC, Bruneau BG, Schinzel A, Seidman JG, Seidman CE, Jorde LB. Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. Nat Genet. 1997 Jul; 16(3):311-5.
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Ogawa T, Linz W, Stevenson M, Bruneau BG, Kuroski de Bold ML, Chen JH, Eid H, Schölkens BA, de Bold AJ. Evidence for load-dependent and load-independent determinants of cardiac natriuretic peptide production. Circulation. 1996 Jun 1; 93(11):2059-67.
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Bruneau BG, Piazza LA, de Bold AJ. Alpha 1-adrenergic stimulation of isolated rat atria results in discoordinate increases in natriuretic peptide secretion and gene expression and enhances Egr-1 and c-Myc expression. Endocrinology. 1996 Jan; 137(1):137-43.
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Yokota N, Bruneau BG, Fernandez BE, de Bold ML, Piazza LA, Eid H, de Bold AJ. Dissociation of cardiac hypertrophy, myosin heavy chain isoform expression, and natriuretic peptide production in DOCA-salt rats. Am J Hypertens. 1995 Mar; 8(3):301-10.
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Yokota N, Bruneau BG, Kuroski de Bold ML, de Bold AJ. Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon. Evidence for a guanylate cyclase-mediated pathway. J Clin Invest. 1994 Nov; 94(5):1938-46.
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Bruneau BG, de Bold AJ. Selective changes in natriuretic peptide and early response gene expression in isolated rat atria following stimulation by stretch or endothelin-1. Cardiovasc Res. 1994 Oct; 28(10):1519-25.
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