Human-mouse differences in the embryonic expression patterns of developmental control genes and disease genes.
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.
Fougerousse
F
F
URA-CNRS 1922-Généthon, 1 rue de l'Internationale, BP 60, 91002 Evry, France.
Bullen
P
P
Herasse
M
M
Lindsay
S
S
Richard
I
I
Wilson
D
D
Suel
L
L
Durand
M
M
Robson
S
S
Abitbol
M
M
Beckmann
J S
JS
Strachan
T
T
D020121:5' Untranslated Regions / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology; D002154:Calpain / Q000096:biosynthesis / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005796:Genes; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D013045:Species Specificity; D051153:Wnt Proteins
D020121:5' Untranslated Regions; D007527:Isoenzymes; D009124:Muscle Proteins; D010446:Peptide Fragments; D011506:Proteins; D011518:Proto-Oncogene Proteins; C092778:WNT7A protein, human; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; C105884:CAPN3 protein, human; D002154:Calpain; C491373:Capn3 protein, mouse