The common fruit fly which is extensively used in the study of genetics developmental biology and neurobiology

There are over 3000 different species of Drosophilidae (Greek for 'dew lovers'), but none is as popular as Drosophila melanogaster, which became the pet organism of geneticists already a century ago (melanogaster is 'black belly' in Greek, referring to the colour of the male's bottom). The term 'fruit fl/ is a misnomer, because Drosophila are actually after the yeast that flourishes on rotten fruit rather than after the fruit itself. D. melanogaster was one of the first organisms to be adapted and then bred purposely for scientific needs. It was introduced into the laboratory by Castle at Harvard in 1901. This was soon followed by Lutz, Loeb, Morgan, and others (Kohler 1994). The major D. melanogaster wild types currently in use date from the 1920s (Ashburner 1989).

What is it that has endowed Drosophila with such a successful career in science?1 Fruit flies are not only cute (at least in the eyes of drosophilists). They are also conveniently small, remarkably inexpensive, clean, harmless (except occasional allergies), and easy to cultivate. Their generation time is only about 10 days at 25°C, and the life cycle includes easily identifiable "phases (Ashburner 1989). Furthermore, Drosophila display a rich, hectic behavioural repertoire, including positive phototaxis (movement towards light), negative geotaxis (movement away from the centre of gravity), and gracious courtship. All these attributes sufficed to convince professors at the turn of the twentieth century to use fruit flies in demonstrations of "development and behaviour.

But it is the amenability of Drosophila to genetic analysis that has made the real difference. The diploid chromosome number of D. melanogaster is only four, including the sex chromosomes X and Y (XX is female, XY male). The giant chromosomes in the larval salivary are real cytological gems. The small number of chromosomes, the convenient chromosomal cytology, the availability of wild types and spontaneous mutants, the short generation time and ease of breeding—all these initiated a meticulous, systematic analysis of Drosophila genetics. With time, the accumulation of knowledge, the large number of genetically mapped mutations, and the rich repertoire of experimental "methods, have all reinforced the experimental advantages of Drosophila, and made it very popular in the study of genetics in multicellular organisms.2 Naturally, the genome of Drosophila was one of the first to be sequenced in the Genome project (13 600 genes, many more transcription units; Adams et al. 2000).

The experimental advantages of Drosophila have also attracted animal psychologists and neurobiologists. Initially, polygene analysis was used to assess the contribution of genes to behaviour (e.g. Hirsch 1959). The field has advanced into a new phase with the use of single-gene mutations; the basic idea was to treat the flies as 'atoms' of genetics and behaviour (Benzer 1967). In the pre-genetic engineering era, the mutants were generated at random, usually by feeding the flies with mutagenic chemicals (Ashbruner 1989). Nowadays, mutations are induced by using virus-like transposable genetic elements that mutate the fly by jumping into its chromosomes, or by other sophisticated methods (e.g. Yin et al. 1995; Goodwin et al. 1997). The putative mutants are then screened for abnormal performance in discrete behavioural tasks, ranging from phototaxis and geotaxis, via courtship, to sensory discrimination. Even in a species that is readily amenable to genetic analysis, the neurogenetics of memory is clearly useless unless efficient, reproducible memory "assays are available. Luckily enough, when presented with the appropriate problems, fruit flies do prove to be surprisingly intelligent. Paradigms of "habituation, "sensitization, and "classical and "instrumental conditioning are now available, involving use-dependent modification of the response of Drosophila to odour, taste, light, touch, potential mates, and "context (Quinn et al. 1974; Tully and Quinn 1985; Hall 1986; Dudai 1988; Corfas and Dudai 1989; Rees and Spatz 1989; Liu et al. 1999).

A number of single gene mutants in Drosophila affect learning and memory rather specifically (Dudai et al. 1976; Aceves-Pina et al. 1983; Dudai 1988; Boynton and Tully 1992; Folkers et al. 1993; Dubnau and Tully 1998; Pinto et al. 1999; DeZazzo et al. 2000). The modifier 'rather' that precedes 'specifically' in the above sentence is critical; whenever one deals with the effect of mutations (or drugs) on learning and memory, the issue of specificity comes up. Because biological memory systems share molecular and cellular processes with other systems in the organism, no absolute specificity should be expected. Memory mutants in Drosophila do display some nonmemory defects (Dudai 1988; Corfas and Dudai 1990; Zhong et al. 1992; Preat 1998). The critical question is, however, whether the mutation still provides useful information on the phenomena, processes, and mechanisms of learning and memory. The answer in many cases is yes. Several mutations, including some that impair the function of "intracellular signal trans-duction cascades, have provided unique insight into the neurobiology of learning and memory (Figure 27). In particular, Drosophila neurogenetics has provided independent and remarkable evidence in support of the role of the so-called cyclic adenosine monophosphate (cAMP) signal transduction cascade in learning and memory (see also "Aplysia, *CREB). It has also been useful in dissecting phases of "acquisition and "consolidation of memory (Dudai 1988; DeZazzo and Tully 1995). And on top of it all, studies in Drosophila have contributed to the identification of the intimate mechanistic links between developmental and behavioural plasticity (e.g. Corfas and Dudai 1991; Schuster et al. 1996).

Attempts have also been made to identify functional centres, neuronal circuits, and the individual neurons that subserve memory in the central nervous system

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