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

Abstract

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.

SLC25A12 expression is associated with neurite outgrowth and is upregulated in the prefrontal cortex of autistic subjects

“…49 Our results and published data show that the spatiotemporal regulation of human SLC25A12 expression evolved from that for the mouse ortholog, as already described for other encoding neuron-specific proteins. 50 A prenatal pattern of expression in regions involved in social cognition Quantitative ISH revealed the existence of three gradients of SLC25A12 expression in the developing neocortex, which we were able to measure. At 8 weeks, a decreasing gradient of expression from the posterior to the anterior of the telencephalon was observed, similar to that reported for several transcription factor genes, such as TBR1, EMX1 and LHX2, and for genes encoding the EphA family of receptor tyrosine kinases in fetal macaque brain.…”

NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome

“…Because embryonic expression can differ substantially between some human-mouse orthologs 14 , we carried out NIPBL in situ hybridization analyses on human embryonic tissue sections. The observed expression pattern was largely consistent with the CdLS phenotype (Figs.…”

Pancreatic Stem Cells: Unresolved Business

“…All islet cells are detectable at the end of the first trimester in humans (Piper et al, 2004), but at later stages in mice (Herrera et al, 1991). These data indicate a human-mouse temporal difference in lineage development (Richardson et al, 1997), and this is supported by differences in gene expression patterns during developmental and disease processes in these two species (Fougerousse et al, 2000). More reviews of human pancreas development can be found elsewhere (De Krijger et al, 1992;Lukinius et al, 1992;Polak et al, 2000).…”