Selected Aspects of Homeobox Gene Function during Mammalian Development.

Abstract

The genetic pathways of development are only beginning to be revealed. But the tools now exist to allow the rapid isolation of genes that carry sequence motifs such as the homeobox, zinc finger or basic-helix loop helix that can mark genes of special developmental significance. Expression patterns are readily determined by in situ hybridization and in vivo developmental functions can be analyzed by generating mice with targeted mutations. Upstream regulators of genes can be identified by finding proteins that bind to cis-regulatory elements. Downstream targets are more difficult to find but there are polymerase chain reaction approaches to define sequences bound by transcription factors and subtractive library approaches to finding specific targets. Although an enormous amount of work remains to be done it is clear that the basic techniques necessary to understand the genetic program of mammalian development are now available. As these techniques are applied and refined we will elaborate the genetic regulatory pathways of organogenesis. This will be deeply satisfying from an intellectual perspective. It will also lead to a better understanding of birth defects and to better treatments of a variety of diseases that involve organ malformation or deterioration. Copyright 1994 S. Karger AG, Basel