Development(s) in mouse genetics

Abstract

Introduction After more than 50 years of classical genetics, developmental genetics of the mouse has entered a new phase. The recent advances in molecular biology enable the old questions in developmental biology to be addressed with new methods. Traditionally, mouse genetics has centered around the study of a large number of mutants that either occurred spontaneously or were induced by experimental mutagenesis. The biological questions that were asked were mainly dictated by the nature of the mutants available. Although phenotypic consequences of mutated genes could be analyzed, the nature of the genes themselves remained unknown. Reverse genetics has changed this situation dramatically. We now have many genes at hand whose functions remain to be discovered. A major focus is on the identification and analysis of developmental control genes in vertebrates. Genetic and molecular studies of developmental processes in Drosophila melanogaster have revealed that embryogenesis is under the control of a cascade of genes directing developmental decisions and orchestrating complex processes, such as cell commitment and differentiation. Mutations affecting the formation of metameric units (segmentation genes) or the identity of segments (homeotic genes) facilitated the identification of a gene regulatory network in which a limited number of key regulatory genes control developmental pathways in the fruit fly (Gehring and Hiromi, Annu. Rev. Genet., 20, 147-173, 1986; Akam, Development (Cambridge), 101, 1-22, 1987; Ingham, Nature (London), 335, 25-34, 1988). Is vertebrate embryogenesis, likewise, under the control of similar genes? The cloning of Drosophila homeotic and segmentation genes has identified at least three types of conserved sequence motifs among these developmental control genes. Low stringency cross-hybridization strategies then led to the identification of a large number of vertebrate genes that have also conserved these sequences. The question therefore arises whether the homeobox, paired-box, and zinc-finger containing genes of the mouse play a similar role in development as their counterparts in Drosophila. To answer this question, three approaches are currently being pursued in the functional analysis of candidate mouse development control genes.