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Human Molecular Genetics, 2000, Vol. 9, No. 2 165-173
© 2000 Oxford University Press

Human–mouse differences in the embryonic expression patterns of developmental control genes and disease genes

Francoise Fougerousse1,2,+, Philip Bullen3,+, Muriel Herasse1, Susan Lindsay3, Isabelle Richard1, David Wilson3, Laurence Suel1,2, Muriel Durand1,2, Steve Robson3, Marc Abitbol4, Jacques S. Beckmann1 and Tom Strachan3,§

1URA-CNRS 1922—Généthon, 1 rue de l’Internationale, BP 60, 91002 Evry, France, 2Laboratoire de Histoembryologie et de Cytogénétique, Faculté Cochin Port Royal, Paris 75014, France, 3Human Genetics Unit, School of Biochemistry and Genetics, University of Newcastle upon Tyne, UK and 4Certo, Faculté Necker, 156 rue de Vaugirard, 75015 Paris, France

Our understanding of early human development has been impeded by the general difficulty in obtaining suitable samples for study. As a result, and because of the extraordinarily high degree of evolutionary conservation of many developmentally important genes and developmental pathways, great reliance has been placed on extrapolation from animal models of development, principally the mouse. However, the strong evolutionary conservation of coding sequence for developmentally important genes does not necessarily mean that their expression patterns are as highly conserved. The very recent availability of human embryonic samples for gene expression studies has now permitted for the first time an assessment of the degree to which we can confidently extrapolate from studies of rodent gene expression patterns. We have found significant human–mouse differences in embryonic expression patterns for a variety of genes. We present detailed data for two illustrative examples. Wnt7a, a very highly conserved gene known to be important in early development, shows significant differences in spatial and temporal expression patterns in the developing brain (midbrain, telencephalon) of man and mice. CAPN3, the locus for LGMD2A limb girdle muscular dystrophy, and its mouse orthologue differ extensively in expression in embryonic heart, lens and smooth muscle. Our study also shows how molecular analyses, while providing explanations for the observed differences, can be important in providing insights into mammalian evolution.

+ These authors contributed equally to this work

§ To whom correspondence should be addressed. Tel: +44 191 222 8855; Fax: +44 191 222 6662; Email: tom.strachan@ncl.ac.uk


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