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Published 5 January 2004. doi:10.1083/jcb.200309160
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 1, 97-109
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Article

 Oriented clonal cell growth in the developing mouse myocardium underlies cardiac morphogenesis

Sigolène M. Meilhac1, Milan Esner1, Michel Kerszberg2, Julie E. Moss3 and Margaret E. Buckingham1

1 Département de Biologie du Développement, Institut Pasteur, Centre National de la Recherche Scientifique (CNRS) URA 2578, 75724 Paris Cedex 15, France
2 Systématique, Adaptation, Évolution, CNRS UMR 7138, Université Pierre et Marie Curie, 75252 Paris Cedex 05, France
3 Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, Scotland, UK

Address correspondence to Margaret E. Buckingham, Département de Biologie du Développement, Institut Pasteur, 28 Rue de Dr. Roux, 75724 Paris Cedex 15, France. Tel.: 33-1-45-68-84-74. Fax: 33-1-40-61-34-52. email: margab{at}pasteur.fr

During heart morphogenesis, cardiac chambers arise by differential expansion of regions of the primitive cardiac tube. This process is under the control of specific transcription factors such as Tbx5 and dHAND. To gain insight into the cellular mechanisms that underlie cardiogenesis, we have used a retrospective clonal approach based on the spontaneous recombination of an nlaacZ reporter gene targeted to the murine {alpha}-cardiac actin locus. We show that clonal growth of myocardial cells is oriented. At embryonic day (E) 10.5, the shape of clones is characteristic of a given cardiac region and reflects its morphology. This is already detectable in the primitive cardiac tube at E8.5, and is maintained after septation at E14.5 with additional modulations. The clonal analysis reveals new subdivisions of the myocardium, including an interventricular boundary region. Our results show that the myocardium, from the time of its formation, is a polarized and regionalized tissue and point to the role of oriented clonal cell growth in cardiac chamber morphogenesis.

Key Words: mouse heart morphogenesis; myocardium; oriented clonal cell growth; laacZ; clonal analysis

Abbreviations used in this paper: {alpha}c-actin, {alpha}-cardiac actin; E, embryonic day.


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