Neural Development in Drosophila 
postdoctoral fellow in our laboratory, found a so- 
lution to this difficulty. 
He modified the enhancer trap method we 
used previously by replacing the /3-galactosidase 
(/3-gaI) reporter gene with a kinesin-|8-gal fusion 
gene. The idea is that the kinesin part of the fu- 
sion protein will drag /3-gaI down the axon to the 
terminal. The idea works very nicely. We have 
-now generated over a thousand enhancer trap 
lines with kinesin-/«cZ as a reporter gene and, in 
more than a hundred of those, have labeled sub- 
sets of CNS and/or PNS pathways, including sen- 
sory and/or motor projections. We would like to 
choose a small number of lines that reveal simple 
axonal pathways (e.g., sensory neuron or motor 
neuron pathways) as a basis for a mutant screen. 
Based on sequence information of a number of 
genes involved in neural development, it seems 
that the majority of these genes contain a previ- 
ously identified functional motif — e.g., the EGF 
repeat found in Notch, the tyrosine kinase do- 
main in sevenless, the homeodomain in cut, and 
the helix-loop-helix motif in da and AS-C In 
each case the existence of such a motif immedi- 
ately provides strong suggestions for the likely 
mode of gene action, which may be tested 
experimentally. 
The existence of readily identifiable motifs in 
the majority of genes involved in neural develop- 
ment suggests that cells have a limited repertoire 
of mechanisms for essential regulatory functions. 
These include various signaling systems, such as 
ligands, receptors, second messenger systems, 
and regulators of gene expression. Perhaps only a 
modest number of new tools had to be invented 
for the formation of the nervous system. Many of 
the cellular mechanisms used in neural develop- 
ment may already have been available before the 
nervous system evolved. Understanding neural 
development may require an understanding of 
the usage and manipulations of these basic func- 
tional motifs. 
It is also apparent that many functional motifs 
have been highly conserved during evolution. 
Several hundred million years separate the in- 
sects and vertebrates, yet the aforementioned mo- 
tifs (the EGF repeat, tyrosine kinase domain, ho- 
meodomain, helix-loop-helix) are common to 
both and remarkably enduring. Thus studying de- 
velopment in the simpler organisms with well- 
developed genetics, such as the fruit fly and the 
nematode, may provide valuable background for 
the investigation of corresponding problems in 
higher forms. 
To follow the development of a nerve 
cell, the neurobiologist will typically 
inject it with a tracer dye. In view of the 
minuteness of the fruit fly embryo, how- 
ever, a method was developed to cause 
the fly to fill its own neurons with a 
marker. A bacterial enzyme was tar- 
geted to nerve processes by fusing the 
gene for kinesin, a molecular motor, to 
the gene encoding fi-galactosidase, an 
enzyme for which there are simple col- 
orimetric assays, and Drosophila stocks were established that express the fusion protein. The 
example shown here displays the pattern seen when the protein is made in all the neurons of the 
embryo. The central ladder-like structure comprises the axons of the ventral nerve cord, and the 
fine lateral extensions are the peripheral neurons and axons. 
Research and photograph by Ed Giniger in the laboratory ofYuh Nungjan. 
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