TEAM

Genetic control of heart development

Group leader : R. Kelly

Our team studies heart development in order to identify biological mechanisms underlying organogenesis, regeneration and congenital disease.

FOR BEGINNERS

Learning how organs form in the embryo is essential to understand the origins of congenital disease and to develop approaches for repairing adult tissue after damage. The heart is the first organ to form and function in the embryo and cardiac development involves complex interactions between genes, progenitor cell populations and inter-cellular signaling events. This complexity is reflected in the fact that congenital heart defects affect 1 in 100 births. Our group studies heart development in the mouse, where the developmental sequence of events is very similar to that in humans, focusing on two critical areas.

Firstly, we investigate the growth of the embryonic heart by progressive addition of myocardium from progenitor cells known as the second heart field (SHF). SHF derived parts of the heart are hotspots for common congenital heart defects. We study the properties of SHF cells and the mechanisms driving their deployment to the heart. The genetic program of the SHF is shared with head muscle progenitor cells, and we also investigate how a common program diverges to give rise to heart and head muscle.

Robert Kelly Team studying cardiac and heart development cardiac stem cell and digeorge syndrome at IBDM, IBDML

Cartoon showing addition of second heart field progenitor cells (blue) to the arterial and venous poles of the heart tube between embryonic days (E) 7.5 and 10.5 of mouse development.

The cardiac conduction system drawing, by Robert Kelly team, for the cardiax and heart development comprehension.

Cartoon showing the specialised cardiac conduction system: yellow, sinoatrial node or pacemaker; blue, atrioventricular node; green, ventricular conduction system. White arrows indicate the direction of electrical conduction.

Secondly, we study the development of the cardiac conduction system that forms the electrical wiring of the heart and coordinates the heartbeat. The conduction system is derived from common progenitor cells with contractile cardiomyoctyes of the heart and we investigate the cellular and genetic mechanisms required for the establishment of these specialized myocytes during normal development and under pathological conditions.

FOR SPECIALISTS

Our group addresses how different progenitor cell populations contribute to the spatial and functional diversity of cardiomyocytes in the mouse heart. An in depth knowledge of heart development is essential to understand the origins of congenital heart disease (CHD) and to promote the repair of damaged heart tissue. We focus on (1) second heart field (SHF) progenitor cell development and (2) the emergence of specialized cardiomyocytes of the ventricular conduction system.

1. Second heart field cardiac progenitor cells

The SHF, identified 20 years ago, is a population of cardiac progenitor cells in pharyngeal mesoderm of the early embryo that gives rise to the right ventricle and outflow tract at the arterial pole of the heart, and atrial myocardium at the venous pole. Perturbation of SHF deployment impacts on later stages of development and leads to defects in atrial, ventricular and outflow tract septation that account for the majority of CHDs.

Our research project focuses on the genetic regulation, epithelial nature and dynamic behavior of SHF cells in the early embryo. Different regions of the heart are pre-patterned within the SHF and we use mouse genetics to study gene function and lineage contributions, together with quantitative imaging, embryo and explant culture, and transcriptomic approaches. We focus on how the regulatory factor TBX1 controls development of a subpopulation of SHF cells that give rise to myocardium at the arterial pole of the heart. TBX1 is the major candidate gene for 22q11.2 deletion (or DiGeorge) syndrome (1 in 4000 live births), a common cause of outflow tract malformations in man. We are investigating the mechanisms that regulate the segregation of SHF cells into TBX1 positive arterial pole progenitor cells and venous pole progenitors, expressing a second T-box gene TBX5, mutations in which cause Holt-Oram syndrome. Moreover we are addressing the currently poorly understood mechanisms by which atrial and ventricular septal structures arise at the interface between TBX1 and TBX5 expressing progenitor populations.

Pharyngeal mesoderm is the source not only of cardiac muscle but also of a subset of skeletal muscles of the head and neck, known as branchiomeric muscles. These muscles are specified in the core of the pharyngeal arches at midgestation and regulate jaw opening and closure, facial expression and pharyngeal and laryngeal function. They differ fundamentally from somite derived muscles that constitute the body and limb musculature. Branchiomeric skeletal muscle progenitor cells are dependent on Tbx1 and develop from a common cardiopharyngeal progenitor population with SHF derived parts of the heart. Our experiments address how divergent myogenic fates arise within this cardiocraniofacial developmental field.

RNAscope fluorescent in situ hybridisation of a mouse embryo at embryonic day 7.5 showing early cardiomyocytes (red) and cardiopharyngeal mesoderm (green).

RNAscope fluorescent in situ hybridisation of a mouse embryo at embryonic day 7.5 showing early cardiomyocytes (red) and cardiopharyngeal mesoderm (green).

2. Wiring the ventricles

The ventricular conduction system (VCS) coordinates the heartbeat and ensures rapid transmission of the electrical signal to the apex of the heart to initiate ventricular contraction. We are using clonal analysis and genetic tracing to study the development of these specialized cardiomyocytes. We are also generating and characterizing mouse models with defective conduction system morphology and function. We are focusing on the development of trabeculae, transient sponge-like myocardial projections in the fetal heart, which represent progenitor cells of the VCS. Persistence of trabeculae results in ventricular non-compaction, associated with conduction anomalies, in human patients.

Polyclonal growth of the ventricular conduction system.

Polyclonal growth of the ventricular conduction system.


Selected publications

PUBLICATION

Capturing Cardiogenesis in Gastruloids

Giuliana Rossi, Nicolas Broguiere, Matthew Miyamoto, Andrea Boni, Romain Guiet, Mehmet Girgin, Robert G Kelly, Chulan Kwon, Matthias P Lutolf
Cell Stem Cell . 2021 Feb 4;28(2):230-240.e6. doi: 10.1016/j.stem.2020.10.013. PMID: 33539223

PUBLICATION

Nkx2-5 defines distinct scaffold and recruitment phases during formation of the murine cardiac Purkinje fiber network

Caroline Choquet, Robert G Kelly, Lucile Miquerol
Nat Commun . 2020 Oct 20;11(1):5300. doi: 10.1038/s41467-020-19150-9. PMID: 33082351

PUBLICATION

Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation

Sonia Stefanovic, Brigitte Laforest, Jean-Pierre Desvignes, Fabienne Lescroart, Laurent Argiro, Corinne Maurel-Zaffran, David Salgado, Elise Plaindoux, Christopher De Bono, Kristijan Pazur, Magali Théveniau-Ruissy, Christophe Béroud, Michel Puceat, Anthony Gavalas, Robert G Kelly, Stephane Zaffran
Elife . 2020 Aug 17;9:e55124. doi: 10.7554/eLife.55124 PMID: 32804075

PUBLICATION

Cardiopharyngeal mesoderm origins of musculoskeletal and connective tissues in the mammalian pharynx.

Adachi N, Bilio M, Baldini A, Kelly RG.
Development. 2020 Feb 3;147(3). PMID: 32014863

PUBLICATION

Tbx1 regulates extracellular matrix-cell interactions in the second heart field

Daniela Alfano, Alessandra Altomonte, Claudio Cortes, Marchesa Bilio, Robert G Kelly, Antonio Baldini
Hum Mol Genet . 2019 Jul 15;28(14):2295-2308. doi: 10.1093/hmg/ddz058 PMID: 31180501

PUBLICATION

A single-cell transcriptional roadmap for cardiopharyngeal fate diversification

Wei Wang, Xiang Niu, Tim Stuart, Estelle Jullian, William M Mauck 3rd, Robert G Kelly, Rahul Satija, Lionel Christiaen
Nat Cell Biol . 2019 Jun;21(6):674-686. doi: 10.1038/s41556-019-0336-z. Epub 2019 Jun 3. PMID: 31160712

PUBLICATION

Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues

Eglantine Heude, Marketa Tesarova, Elizabeth M Sefton, Estelle Jullian, Noritaka Adachi, Alexandre Grimaldi, Tomas Zikmund, Jozef Kaiser, Gabrielle Kardon, Robert G Kelly, Shahragim Tajbakhsh
Elife . 2018 Nov 19;7:e40179. doi: 10.7554/eLife.40179 PMID: 30451684

PUBLICATION

T-box genes and retinoic acid signaling regulate the segregation of arterial and venous pole progenitor cells in the murine second heart field

Christopher De Bono, Charlotte Thellier, Nicolas Bertrand, Rachel Sturny, Estelle Jullian, Claudio Cortes, Sonia Stefanovic, Stéphane Zaffran, Magali Théveniau-Ruissy, Robert G Kelly
Hum Mol Genet . 2018 Nov 1;27(21):3747-3760. doi: 10.1093/hmg/ddy266 PMID: 30016433

PUBLICATION

Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy

Caroline Choquet, Thi Hong Minh Nguyen, Pierre Sicard, Emeline Buttigieg, Thi Thom Tran, Frank Kober, Isabelle Varlet, Rachel Sturny, Mauro W Costa, Richard P Harvey, Catherine Nguyen, Pascal Rihet, Sylvain Richard, Monique Bernard, Robert G Kelly, Nathalie Lalevée, Lucile Miquerol
PLoS Genet . 2018 Jul 6;14(7):e1007502. doi: 10.1371/journal.pgen.1007502. eCollection 2018 Jul. PMID: 29979676

PUBLICATION

Diverging roads to the heart

Robert G Kelly, Silke R Sperling
Science . 2018 Mar 9;359(6380):1098-1099. doi: 10.1126/science.aat0230 PMID: 29590027

PUBLICATION

Epithelial Properties of the Second Heart Field

Claudio Cortes, Alexandre Francou, Christopher De Bono, Robert G Kelly
Circ Res . 2018 Jan 5;122(1):142-154. doi: 10.1161/CIRCRESAHA.117.310838 PMID: 29301846

PUBLICATION

Epithelial tension in the second heart field promotes mouse heart tube elongation.

Francou A, De Bono C, Kelly RG.
Nat Commun. 2017 Mar 30;8:14770. PMID: 28357999

PUBLICATION

Endothelial Plasticity Drives Arterial Remodeling Within the Endocardium After Myocardial Infarction

Miquerol L, Thireau J, Bideaux P, Sturny R, Richard S, Kelly RG.
Circ Res. 2015 May 22;116(11):1765-71. PMID: 25834185

PUBLICATION

A new heart for a new head in vertebrate cardiopharyngeal evolution.

Diogo R, Kelly RG, Christiaen L, Levine M, Ziermann JM, Molnar JL, Noden DM, Tzahor E.
Nature. 2015 Apr 23;520(7548):466-73. PMID: 25903628

PUBLICATION

FGF10 promotes regional foetal cardiomyocyte proliferation and adult cardiomyocyte cell-cycle re-entry.

Rochais F, Sturny R, Chao CM, Mesbah K, Bennett M, Mohun TJ, Bellusci S, Kelly RG.
Cardiovasc Res. 2014 Dec 1;104(3):432-42. PMID: 25344367

PUBLICATION

TBX1 regulates epithelial polarity and dynamic basal filopodia in the second heart field.

Francou A, Saint-Michel E, Mesbah K, Kelly RG.
Development. 2014 Nov;141(22):4320-31. doi: 10.1242/dev.115022. PMID: 25371366

PUBLICATION

Tbx1 Coordinates Addition of Posterior Second Heart Field Progenitor Cells to the Arterial and Venous Poles of the Heart.

Rana MS, Théveniau-Ruissy M, De Bono C, Mesbah K, Francou A, Rammah M, Domínguez JN, Roux M, Laforest B, Anderson RH, Mohun T, Zaffran S, Christoffels VM, Kelly RG.
Circ Res. 2014 Oct 10;115(9):790-9. PMID: 25190705

PUBLICATION

Organogenesis of the vertebrate heart.

Miquerol L, Kelly RG.
Wiley Interdiscip Rev Dev Biol. 2013 Jan;2(1):17-29. PMID: 23799628

PUBLICATION

The second heart field.

Kelly RG.
Curr Top Dev Biol. 2012;100:33-65. PMID: 22449840

PUBLICATION

Biphasic development of the mammalian ventricular conduction system.

Miquerol L, Moreno-Rascon N, Beyer S, Dupays L, Meilhac SM, Buckingham ME, Franco D, Kelly RG.
Circ Res. 2010 Jul 9;107(1):153-61. PMID: 20466980

PUBLICATION

Integrating Matrix Signals During Arch Artery Morphogenesis

Robert G Kelly
Circ Res . 2021 Feb 5;128(3):360-362. doi: 10.1161/CIRCRESAHA.121.318669. PMID: 33539223

PUBLICATION

A Second Heart Field-Derived Vasculogenic Niche Contributes to Cardiac Lymphatics

Ghislaine Lioux, Xiaolei Liu, Susana Temiño, Michael Oxendine, Estefanía Ayala, Sagrario Ortega, Robert G Kelly, Guillermo Oliver, Miguel Torres
Dev Cell . 2020 Feb 10;52(3):350-363.e6. doi: 10.1016/j.devcel.2019.12.006. Epub 2020 Jan 9. PMID: 31928974

PUBLICATION

Straightjacket/α2δ3 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1

Emilie Auxerre-Plantié, Masayuki Nakamori, Yoan Renaud, Aline Huguet, Caroline Choquet, Cristiana Dondi, Lucile Miquerol, Masanori P Takahashi, Geneviève Gourdon, Guillaume Junion, Teresa Jagla, Monika Zmojdzian, Krzysztof Jagla
Elife . 2019 Dec 12;8:e51114. doi: 10.7554/eLife.51114 PMID: 31829940

PUBLICATION

Defects in Trabecular Development Contribute to Left Ventricular Noncompaction

Caroline Choquet, Robert G Kelly, Lucile Miquerol
Pediatr Cardiol . 2019 Oct;40(7):1331-1338. doi: 10.1007/s00246-019-02161-9. PMID: 31342111

PUBLICATION

Loss of Tbx3 in murine neural crest reduces enteric glia and causes cleft palate, but does not influence heart development or bowel transit

Silvia Huerta López, Marina Avetisyan, Christina M Wright, Karim Mesbah, Robert G Kelly, Anne M Moon, Robert O Heuckeroth
Dev Biol . 2018 Dec 1;444 Suppl 1(Suppl 1):S337-S351. doi: 10.1016/j.ydbio.2018.09.017 PMID: 30292786

PUBLICATION

Embryonic Tbx3 + cardiomyocytes form the mature cardiac conduction system by progressive fate restriction

Rajiv A Mohan, Mathilda T M Mommersteeg, Jorge N Domínguez, Caroline Choquet, Vincent Wakker, Corrie de Gier-de Vries, Gerard J J Boink, Bastiaan J Boukens, Lucile Miquerol, Arie O Verkerk, Vincent M Christoffels
Development . 2018 Sep 3;145(17):dev167361. doi: 10.1242/dev.167361 PMID: 30042181

PUBLICATION

How Mesp1 makes a move

Kelly RG.
J Cell Biol. 2016 May 23;213(4):411-3. PMID: 27185831

PUBLICATION

Coronary stem development in wildtype and Tbx1 null mouse hearts.

Théveniau-Ruissy M, Pérez-Pomares JM, Parisot P, Baldini A, Miquerol L, Kelly RG.
Dev Dyn. 2015 Dec 28. doi: 10.1002/dvdy.24380. PMID: 26708418

PUBLICATION

Revascularization of the heart after infarct: lessons from embryonic development.

Miquerol L.
Med Sci (Paris). 2016 Feb;32(2):158-62. PMID: 26936172

PUBLICATION

Congenital coronary artery anomalies: a bridge from embryology to anatomy and pathophysiology--a position statement of the development, anatomy, and pathology ESC Working Group.

Pérez-Pomares JM, de la Pompa JL, Franco D, Henderson D, Ho SY, Houyel L, Kelly RG, Sedmera D, Sheppard M, Sperling S, Thiene G, van den Hoff M, Basso C.
Cardiovasc Res. 2016 Feb 1;109(2):204-16. PMID: 26811390

PUBLICATION

A Cranial Mesoderm Origin for Esophagus Striated Muscles.

Gopalakrishnan S, Comai G, Sambasivan R, Francou A, Kelly RG, Tajbakhsh S.
Dev Cell. 2015 Sep 28;34(6):694-704. PMID: 26387456

PUBLICATION

Adhesive Enrichment and Membrane Turnover at the Heart of Cardiopharyngeal Induction.

Kelly RG.
Dev Cell. 2015 Sep 14;34(5):490-2. PMID: 26374763

PUBLICATION

Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2.

Zaglia T, Pianca N, Borile G, Da Broi F, Richter C, Campione M, Lehnart SE, Luther S, Corrado D, Miquerol L, Mongillo M.
Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):E4495-504. PMID: 26204914

PUBLICATION

Loss of Wnt5a disrupts second heart field cell deployment and may contribute to OFT malformations in DiGeorge syndrome.

Sinha T, Li D, Théveniau-Ruissy M, Hutson MR, Kelly RG, Wang J.
Hum Mol Genet. 2015 Mar 15;24(6):1704-16. PMID: 25410658

PUBLICATION

Clonal analysis reveals a common origin between nonsomite-derived neck muscles and heart myocardium.

Lescroart F, Hamou W, Francou A, Théveniau-Ruissy M, Kelly RG, Buckingham M.
Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1446-51. PMID: 25605943

PUBLICATION

Prdm1 functions in the mesoderm of the second heart field, where it interacts genetically with Tbx1, during outflow tract morphogenesis in the mouse embryo

Vincent SD, Mayeuf-Louchart A, Watanabe Y, Brzezinski JA, Miyagawa-Tomita S, Kelly RG, Buckingham M.
Hum Mol Genet. 2014 Oct 1;23(19):5087-101. PMID: 24821700

PUBLICATION

Heart fields and cardiac morphogenesis.

Kelly RG, Buckingham ME, Moorman AF.
Cold Spring Harb Perspect Med. 2014 Oct 1;4(10). PMID: 25274757

PUBLICATION

Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation.

Mesirca P, Alig J, Torrente AG, Müller JC, Marger L, Rollin A, Marquilly C, Vincent A, Dubel S, Bidaud I, Fernandez A, Seniuk A, Engeland B, Singh J, Miquerol L, Ehmke H, Eschenhagen T, Nargeot J, Wickman K, Isbrandt D, Mangoni ME.
Nat Commun. 2014 Aug 21;5:4664. PMID: 25144323

PUBLICATION

Resolving cell lineage contributions to the ventricular conduction system with a Cx40-GFP allele: a dual contribution of the first and second heart fields.

Miquerol L, Bellon A, Moreno N, Beyer S, Meilhac SM, Buckingham M, Franco D, Kelly RG.
Dev Dyn. 2013 Jun;242(6):665-77. PMID: 23526457

PUBLICATION

Second heart field cardiac progenitor cells in the early mouse embryo.

Francou A, Saint-Michel E, Mesbah K, Théveniau-Ruissy M, Rana MS, Christoffels VM, Kelly RG.
Biochim Biophys Acta. 2013 Apr;1833(4):795-8. PMID: 23051926

PUBLICATION

Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium.

Watanabe Y, Zaffran S, Kuroiwa A, Higuchi H, Ogura T, Harvey RP, Kelly RG, Buckingham M.
Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18273-80. PMID: 23093675

PUBLICATION

The effect of connexin40 deficiency on ventricular conduction system function during development.

Sankova B, Benes J Jr, Krejci E, Dupays L, Theveniau-Ruissy M, Miquerol L, Sedmera D.
Cardiovasc Res. 2012 Sep 1;95(4):469-79. PMID: 22739121

PUBLICATION

Epistatic rescue of Nkx2.5 adult cardiac conduction disease phenotypes by prospero-related homeobox protein 1 and HDAC3.

Risebro CA, Petchey LK, Smart N, Gomes J, Clark J, Vieira JM, Yanni J, Dobrzynski H, Davidson S, Zuberi Z, Tinker A, Shui B, Tallini YI, Kotlikoff MI,Miquerol L, Schwartz RJ, Riley PR.
Circ Res. 2012 Jul 6;111(2):e19-31. PMID: 22647876

PUBLICATION

New developments in the second heart field.

Zaffran S, Kelly RG.
Differentiation. 2012 Jul;84(1):17-24. PMID: 22521611

PUBLICATION

Remodeling of the peripheral cardiac conduction system in response to pressure overload.

Harris BS, Baicu CF, Haghshenas N, Kasiganesan H, Scholz D, Rackley MS, Miquerol L, Gros D, Mukherjee R, O'Brien TX.
Am J Physiol Heart Circ Physiol. 2012 Apr 15;302(8):H1712-25. PMID: 22307665

PUBLICATION

Identification of a Tbx1/Tbx2/Tbx3 genetic pathway governing pharyngeal and arterial pole morphogenesis.

Mesbah K, Rana MS, Francou A, van Duijvenboden K, Papaioannou VE, Moorman AF, Kelly RG, Christoffels VM.
Hum Mol Genet. 2012 Mar 15;21(6):1217-29. PMID: 22116936

PUBLICATION

Irx3: a conductor of conduction.

Kelly RG.
Circ Res. 2011 Oct 14;109(9):984-5. PMID: 21998297

PUBLICATION

Contemporary cardiogenesis: new insights into heart development.

Franco D, Kelly RG.
Cardiovasc Res. 2011 Jul 15;91(2):183-4. PMID: 21632879

PUBLICATION

Establishment of the mouse ventricular conduction system.

Miquerol L, Beyer S, Kelly RG.
Cardiovasc Res. 2011 Jul 15;91(2):232-42. PMID: 21385837

PUBLICATION

Tbx1, subpulmonary myocardium and conotruncal congenital heart defects.

Parisot P, Mesbah K, Théveniau-Ruissy M, Kelly RG.
Birth Defects Res A Clin Mol Teratol. 2011 Jun;91(6):477-84. PMID: 21591244

PUBLICATION

Inducible Cx40-Cre expression in the cardiac conduction system and arterial endothelial cells.

Beyer S, Kelly RG, Miquerol L.
Genesis. 2011 Feb;49(2):83-91. PMID: 21344610

PUBLICATION

Core issues in craniofacial myogenesis.

Kelly RG.
Exp Cell Res. 2010 Nov 1;316(18):3034-41. PMID: 20457151

PUBLICATION

Clonal analysis reveals common lineage relationships between head muscles and second heart field derivatives in the mouse embryo.

Lescroart F, Kelly RG, Le Garrec JF, Nicolas JF, Meilhac SM, Buckingham M.
Development. 2010 Oct;137(19):3269-79. PMID: 20823066

PUBLICATION

Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome.

van Bueren KL, Papangeli I, Rochais F, Pearce K, Roberts C, Calmont A, Szumska D, Kelly RG, Bhattacharya S, Scambler PJ.
Dev Biol. 2010 Apr 15;340(2):369-80. PMID: 20122914

PUBLICATION

Decreased levels of embryonic retinoic acid synthesis accelerate recovery from arterial growth delay in a mouse model of DiGeorge syndrome.

Ryckebüsch L, Bertrand N, Mesbah K, Bajolle F, Niederreither K, Kelly RG, Zaffran S.
Circ Res. 2010 Mar 5;106(4):686-94. PMID: 20110535

PUBLICATION

Role of mesodermal FGF8 and FGF10 overlaps in the development of the arterial pole of the heart and pharyngeal arch arteries.

Watanabe Y, Miyagawa-Tomita S, Vincent SD, Kelly RG, Moon AM, Buckingham ME.
Circ Res. 2010 Feb 19;106(3):495-503. PMID: 20035084

PUBLICATION

Megavoltage planar and cone-beam imaging with low-Z targets: dependence of image quality improvement on beam energy and patient separation.

Robar JL, Connell T, Huang W, Kelly RG.
Med Phys. 2009 Sep;36(9):3955-63. PMID: 19810468

PUBLICATION

Hes1 is expressed in the second heart field and is required for outflow tract development.

Rochais F, Dandonneau M, Mesbah K, Jarry T, Mattei MG, Kelly RG.
PLoS One. 2009 Jul 17;4(7):e6267. PMID: 19609448

PUBLICATION

Monitoring clonal growth in the developing ventricle.

Miquerol L, Kelly RG.

PUBLICATION

Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates.

Sambasivan R, Gayraud-Morel B, Dumas G, Cimper C, Paisant S, Kelly RG, Tajbakhsh S.
Dev Cell. 2009 Jun;16(6):810-21. PMID: 19531352

PUBLICATION

Signaling pathways controlling second heart field development.

Rochais F, Mesbah K, Kelly RG.
Circ Res. 2009 Apr 24;104(8):933-42. PMID: 19390062

PUBLICATION

Relationship between neural crest cells and cranial mesoderm during head muscle development.

Grenier J, Teillet MA, Grifone R, Kelly RG, Duprez D.
PLoS One. 2009;4(2):e4381. PMID: 19198652

PUBLICATION

Properties of branchiomeric and somite-derived muscle development in Tbx1 mutant embryos.

Grifone R, Jarry T, Dandonneau M, Grenier J, Duprez D, Kelly RG.
Dev Dyn. 2008 Oct;237(10):3071-8. PMID: 18816853

PUBLICATION

Tbx3 is required for outflow tract development.

Mesbah K, Harrelson Z, Théveniau-Ruissy M, Papaioannou VE, Kelly RG.
Circ Res. 2008 Sep 26;103(7):743-50. PMID: 18723448

PUBLICATION

The del22q11.2 candidate gene Tbx1 controls regional outflow tract identity and coronary artery patterning.

Théveniau-Ruissy M, Dandonneau M, Mesbah K, Ghez O, Mattei MG, Miquerol L, Kelly RG.
Circ Res. 2008 Jul 18;103(2):142-8. PMID: 18583714

PUBLICATION

Integration of embryonic and fetal skeletal myogenic programs at the myosin light chain 1f/3f locus.

Zammit PS, Cohen A, Buckingham ME, Kelly RG.
Dev Biol. 2008 Jan 1;313(1):420-33. PMID: 18062958

PUBLICATION

Myocardium at the base of the aorta and pulmonary trunk is prefigured in the outflow tract of the heart and in subdomains of the second heart field.

Bajolle F, Zaffran S, Meilhac SM, Dandonneau M, Chang T, Kelly RG, Buckingham ME.
Dev Biol. 2008 Jan 1;313(1):25-34. PMID: 18005956

PUBLICATION

Heartening news for head muscle development.

Grifone R, Kelly RG.
Trends Genet. 2007 Aug;23(8):365-9. PMID: 17524520

PUBLICATION

Building the right ventricle.

Kelly RG.
Circ Res. 2007 Apr 13;100(7):943-5. PMID: 17431196

PUBLICATION

Visualization of outflow tract development in the absence of Tbx1 using an FgF10 enhancer trap transgene.

Kelly RG, Papaioannou VE.
Dev Dyn. 2007 Mar;236(3):821-8. http://www.ncbi.nlm.nih.gov/pubmed/17238155

PUBLICATION

From developmental biology to heart repair.

Campione M, Moorman AF, Kelly RG.
Cell Mol Life Sci. 2007 Mar;64(6):643-5. PMID: 17380305

PUBLICATION

Congenital heart defects in Fgfr2-IIIb and Fgf10 mutant mice.

Marguerie A, Bajolle F, Zaffran S, Brown NA, Dickson C, Buckingham ME, Kelly RG.
Cardiovasc Res. 2006 Jul 1;71(1):50-60. PMID: 16687131

PUBLICATION

Left and right ventricular contributions to the formation of the interventricular septum in the mouse heart.

Franco D, Meilhac SM, Christoffels VM, Kispert A, Buckingham M, Kelly RG.
Dev Biol. 2006 Jun 15;294(2):366-75. PMID: 16677630

PUBLICATION

Rotation of the myocardial wall of the outflow tract is implicated in the normal positioning of the great arteries.

Bajolle F, Zaffran S, Kelly RG, Hadchouel J, Bonnet D, Brown NA, Buckingham ME.
Circ Res. 2006 Feb 17;98(3):421-8. PMID: 16397144

PUBLICATION

Molecular inroads into the anterior heart field.

Kelly RG.
Trends Cardiovasc Med. 2005 Feb;15(2):51-6. PMID: 15885570

PUBLICATION

T-box genes in vertebrate development.

Naiche LA, Harrelson Z, Kelly RG, Papaioannou VE.
Annu Rev Genet. 2005;39:219-39. PMID: 16285859

PUBLICATION

The del22q11.2 candidate gene Tbx1 regulates branchiomeric myogenesis.

Kelly RG, Jerome-Majewska LA, Papaioannou VE.
Hum Mol Genet. 2004 Nov 15;13(22):2829-40. PMID: 15385444

PUBLICATION

Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development.

Harrelson Z, Kelly RG, Goldin SN, Gibson-Brown JJ, Bollag RJ, Silver LM, Papaioannou VE.
Development. 2004 Oct;131(20):5041-52. PMID: 15459098

PUBLICATION

The clonal origin of myocardial cells in different regions of the embryonic mouse heart.

Meilhac SM, Esner M, Kelly RG, Nicolas JF, Buckingham ME.
Dev Cell. 2004 May;6(5):685-98. PMID: 15130493

PUBLICATION

Cell history determines the maintenance of transcriptional differences between left and right ventricular cardiomyocytes in the developing mouse heart.

Kelly RG, Lemonnier M, Zaffran S, Munk A, Buckingham ME.
J Cell Sci. 2003 Dec 15;116(Pt 24):5005-13. PMID: 14625394

PUBLICATION

The anterior heart-forming field: voyage to the arterial pole of the heart.

Kelly RG, Buckingham ME.
Trends Genet. 2002 Apr;18(4):210-6. PMID: 11932022

PUBLICATION

The arterial pole of the mouse heart forms from Fgf10-expressing cells in pharyngeal mesoderm.

Kelly RG, Brown NA, Buckingham ME.
Dev Cell. 2001 Sep;1(3):435-40. PMID: 11702954

Interactions

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INTERNATIONAL

Funding

ANR funding for Robert Kelly Team who study cardiac stem cell in mus musculus at IBDM FRM funding for Robert Kelly Team who study cardiac development in mus musculus

Leducq

AFM

Societe-francaise-cancer

Members more

    Julien Fromonot Clara Guijarro Calvo   Lucie Boulgakoff Camille Dumas Lucile Miquerol Rachel Sturny Charlotte Thellier
Robert Kelly
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Robert Kelly

Researcher

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Antonia Boudet

Master - M1

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marie Couderc

MSc student

Julien Fromonot
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Julien Fromonot

Others

Clara Guijarro Calvo
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Clara Guijarro Calvo

PhD student

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Nicolas Bertrand

University lecturer

Lucie Boulgakoff
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Lucie Boulgakoff

PhD student

Camille Dumas
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Camille Dumas

PhD student

Lucile Miquerol
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Lucile Miquerol

Researcher

Lucile’s research projects concern the development of the ventricular conduction system to address the question: how does the heart beat in rhythm? We employ genetic tools to perform lineage analysis of the ventricular conduction system and to study the development of the conduction system in embryos with congenital heart diseases. The use of the Cre-Lox system in combination with conditional reporter mice allows us to visualize and trace the conduction system and its progenitors to understand when these cells diverge from the myocardium and what is happening during pathological conditions.

Rachel Sturny
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Rachel Sturny

Technical staff

Charlotte Thellier
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Charlotte Thellier

PhD student

Alumni

  • Choquet, Caroline: Post-doc, Lescroart lab, Marseille Medical Genetics Unit, Inserm UMR_S910, Medical School, Aix-Marseille University, Marseille
  • De Bono, Christopher: Post-doc, Morrow lab, Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA
  • Francou, Alexandre: Post-doc, Anderson lab, Memorial Sloan Kettering Cancer Center, SKI, Developmental Biology Department, 430 E 67th St, New York, NY10065, USA
  • Jullian, Estelle
  • Mesbah, Karim: Responsable de la plateforme d’exploration fonctionnelle à l’IGF-IGH, Montpellier.
  • Rammah, Mayyasa: Post-doc, Quatar
  • Rochais, Francesca: Group leader, Marseille Medical Genetics Unit, Inserm UMR_S910, Medical School, Aix-Marseille University, Marseille
  • Theveniau-Ruissy, Magali: Research Scientist, Rochais lab, Marseille Medical Genetics Unit, Inserm UMR_S910, Medical School, Aix-Marseille University, Marseille

Overview

Model organism
Biological process studied
  • Heart development
Biological techniques
  • Mouse genetics
  • Molecular and cellualr biology
  • Embryology and Anatomy
  • Embryo and explant culture
  • Spatial and single cells transcriptomics
  • Analysis of cardiac function
Medical applications
  • Congenital heart defects including structural and conduction anomalies and cardiac repair