The homeotic gene products in the control of cell differentiation and proliferation

Embryo development is controlled by a successive series of genes that provide each cell in the growing embryo with precise position information. Knowledge of these genes is known most completely from Drosophila, where a simple initial pattern generated by maternal effect genes is gradually segmented by the sequential transient expression of three successive series of genes: the gap genes, the pair-rule genes, and the segment polarity genes. Superimposing their action on the preexisting segments, these homeotic genes cause unique and often very distinctive patterns of differentiation for different segments. In humans, about 40 homeotic genes have been identified and are grouped into four clusters on chromosomes 2, 7, 12, and 17, whose organization reflects their spatial and temporal expression. Several homeotic genes have been found expressed not only in embryonic tissues, but also in adult tissues, most notably in the hematopoietic lineage, and also in tumors, especially leukemia, teratocarcinoma, and neuroblastoma, wherein their expression pattern is modified in a complex manner by retinoic acid. The target genes of the transcription factors encoded by the homeotic genes are largely unknown, but recent reports indicate that they may regulate the expression of adhesion molecules on the membrane and the production of components of the extracellular matrix. Abnormal expression of these genes can therefore affect not only cell proliferation, but also the spread of cells to aberrant locations.