Molecular Genetics of Neuronal Recognition in Drosophila 
(fas II), fasciclin III (fas III), and neuroglian. 
These glycoproteins are dynamically expressed 
on overlapping subsets of axon fascicles and glia 
during embryonic development. 
Three of these molecules, fas II, fas III, and 
neuroglian, are part of the immunoglobulin su- 
perfamily and are highly related to a family of 
adhesion molecules found on the surface of ver- 
tebrate neurons. The other protein, fas I, appears 
unrelated to any currently listed in the data bank. 
Our molecular genetic analysis has shown that, 
by a process of alternative RNA splicing, all four 
proteins are generated in a variety of different 
forms by different cells during development. To 
begin to test the function of these proteins, we 
used transformation techniques to induce their 
expression on the surface of the S2 Drosophila 
cell line in culture. With standard aggregation as- 
says and biochemical methods, we have shown 
that these four proteins are homophilic adhesion 
molecules that can mediate selective cell sorting 
as well as cell aggregation; apparently fas I de- 
fines a new class of adhesion molecules. 
We are using genetic analysis and transforma- 
tion methods to study the function of these mole- 
cules in the developing organism. We generated 
and identified insertional mutations and small 
deletions in the fas /, fas II, fas III, and neuro- 
glian genes. Complete loss-of-function muta- 
tions in both fas I and fas III are viable under 
laboratory conditions; mutations in fas II and 
neuroglian lead to lethality. None of the four 
mutations lead to gross abnormalities in the devel- 
oping nervous system. Rather, the mutations ap- 
pear to lead to more subtle defects in specific 
subsets of neurons and specific axon pathways. 
For example, the fas II protein is normally ex- 
pressed on a small subset of growth cones and 
axons that pioneer and selectively fasciculate in 
the MPl axon fascicle. In the fas //mutant, these 
specific growth cones do not properly recognize 
one another and the MPl pathway does not form; 
in contrast, other axon pathways appear to de- 
velop normally. Thus this member of the immu- 
noglobulin superfamily functions in part as a neu- 
ronal recognition molecule for the MPl axon 
fascicle. 
Third, we have been identifying and character- 
izing genes that function in the early interactions 
of the glia and mesectoderm in establishing the 
initial patterns of axon pathways or that function 
in the production or reception of the signals that 
attract the commissural growth cones toward the 
midline. For example, several new genes have 
been identified that appear to function in the 
guidance of growth cones toward the midline; 
mutations in these genes specifically disrupt the 
ability of commissural growth cones to extend 
toward and across the midline. 
Fourth, we are using a variety of genetic and 
molecular genetic methods to screen for new 
genes that are involved in target recognition. As a 
model system for the study of target recognition 
in Drosophila, we focus on the ability of moto- 
neuron growth cones to find and recognize their 
correct muscles during embryonic development. 
We have identified several genes that are ex- 
pressed by different subsets of undifferentiated 
muscle fibers prior to innervation. Two of these 
genes encode membrane proteins that are 
members of the same gene family of cell adhesion 
and signaling molecules. We are presently char- 
acterizing mutations in these two genes. 
Opposite: Visualization of axons (brown stain ) and different subsets of glia (blue stain, reveal- 
ing only nuclei) in or just outside the developing central nervous system in the embryo of the fruit 
fly Drosophila melanogaster. The four panels show four different subsets of embryonic glia ( as 
revealed by the "enhancer trap" method) in relation to the pattern of axon pathways that develop 
around them. Panel A shows the midline glia; panel B, the longitudinal glia and several other 
classes of nerve root and exit glia; and panel C, a small subset of these glia — all in relation to the 
pattern of axon pathways in four or five segments of the central nervous system. Panel D shows 
the four exit glia just outside the central nervous system in three segments. 
From Kldmbt, C, and Goodman, C.S. 1991. GLIA 4:205-213. 
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