ABSTRACT
This chapter reviews the application of a modified gene trapping method that permits a systematic phenotypic screen to identify such genes in mice. It introduces the idea of gene trapping and discusses how we have applied it to identify ligands and receptors that regulate neural development. The chapter describes the rationale for modifying the vector in a way that facilitates the identification of brain wiring mechanisms. In gene trapping approaches, large numbers of insertional mutations can be isolated in embryonic stem cells using a deoxyribonucleic acid construct that integrates at random in the genome. Prior to screening for axon guidance defects, heterozygotes are intercrossed and neonatal litters examined for obvious morphological or behavioral defects. In addition to identifying mutants with morphological or neurological defects, a major goal of the screen is to discover novel axon-guidance molecules by studying wiring patterns in mutant animals.
