Isolation of novel developmental genes from human germ cell, oocyte and embryo cDNA by differential display

Due to the difficulties inherent in research on human embryos, almost nothi ng is known about genes active in human early development. Although the hum an genome project will provide resources that theoretically provide access to every human gene, those genes specific to human early development may be difficult to define. Also, by definition, genes specific to early developm ent will not be represented in cDNA databases derived from human somatic ce lls. Yet these unknown human developmental genes are likely to be of key im portance for several areas of human health, including assisted reproduction and contraception, embryo stem cell research and tissue transplantation, a geing and cancer. In order to identify and isolate these human developmenta l genes, we have prepared amplified cDNA from human primordial germ cells, oocytes and embryos, and used differential display to compare patterns of g ene expression in these embryonic cells and in the cells of somatic tissues of a 10-week human fetus. This paper reviews the highly sensitive procedur es used to create amplified cDNA representing expressed genes in a single c ell and the use of differential display to identify developmental genes. Se veral such genes have been isolated, but their full-length sequences and fu nction are yet to be elucidated. Genes active in human early development ar e expected to play key roles in the maintenance of the archetypal stem cell state, potential immortality and the invasiveness of trophectoderm and pri mordial germ cells. They represent candidate genes regulating these functio ns for targeting in clinical research in human reproduction, stem cell diff erentiation and cancer.