The Effect of X-Chromosome Deficiencies on Neurogenesis in Drosophila

Abstract

Complex biological processes, such as the development of the central nervous system (CNS) of Drosophila, can be dissected into logical steps by introducing genetic variations. In the beginning the major difficulty encountered in this process is that of defining the elements involved, which in turn is dependent on obtaining mutants suitable for analysis. The reason for this difficult is twofold: on the one hand, mutants affecting essential aspects of neurogenesis are expected to be lethal; on the other hand, the CNS is an internal structure, and the appraisal of mutant variations requires the use of special techniques. Drosophila goes through different developmental stages, embryonic, larval and pupal, before reaching the final imaginal stage. Assuming a low probability for neurogenic mutants to develop to the imaginal stage, a reasonable way of screening for such mutants is to concentrate on the study of embryos. For neurobiological studies Drosophila embryos are inconvenient because of their small size, which makes selective staining of neurones extremely difficult. However, they offer several important advantages for our purposes: the CNS of mature embryos is roughly comparable to that of third instar larvae, disregarding the proliferation within the imaginal anlagen; techniques have been developed which allow the simultaneous study of dozens of embryos as whole-mounts, in which the CNS can be visualized “in toto”; embryonic lethality can be used as a previous selection criterium. Wright (1970) proposed selecting for embryonic lethal point mutants when searching for mutants affecting embryogenesis; the same strategy could be pursued for studying neurogenic variations since they are probably found among embryonic lethals. However, a few arguments make clear that this approach may be very time consuming. Mutants with embryonic pheno-effective periods have been found in 30% of all point lethals (Hadorn, 1961); furthermore, mutagenesis studies have demonstrated that about 90% of all genes can mutate to lethal conditions (Judd et al., 1972). Accepting that the total number of genes in the chromosomal genome of Drosophila is about 5000 (Lefevre, 1974) a simple calculation indicates that about 1350 genes might show an embryonic lethal phenotype when mutated.