Large-scale Analysis of Genes Regulated during Mouse Placental Development Reveals their Prevalent Localization within Imprinted Chromosomal Regions

Myriam Hemberger
Department of Biochemistry and Molecular Biology; University of Calgary

The placenta is essential for fetal growth and survival and therefore represents a target organ for the growth controlling actions of imprinted genes. This is reflected by the finding that all imprinted genes identified to date are expressed in the placenta. To screen for genes expressed and regulated between early (e7.5) and late (e17.5) stages of mouse placental development, we have applied a combination of cDNA subtraction and array hybridization. A total of 638 clones were identified, 488 with the e7.5-specific probe and 150 with the e17.5-specific probe. Importantly, 56.9% of the hybridizing clones were not known to be expressed in extraembryonic tissues before. Differential expression was confirmed by Northern blot and in situ hybridization for 44/44 clones demonstrating the high efficiency and specificity of cDNA subtraction and array hybridization. For 152 of all 638 hybridizing clones, mapping information was available and revealed a non-random distribution with a prevalence of localization on chromosomes subject to imprinting effects. Specifically, the imprinted regions of chromosomes 2, 6, 7, 9, 12, and 17 harbored 80% of all genes that mapped to these chromosomes. Exceptions were chromosomes 11 and 18 were no gene was localized within the imprinted regions. Interestingly, we also found a clustering of genes on the proximal and central X-chromosome, a region known to be involved in placental growth and development. These data stress the correlation between placental growth control and genomic imprinting and provide a source of genes potentially controlled by genomic imprinting.