MOLECULAR GENETICS OF CELL ADHESION AND CELL RECOGNITION 
DURING NEURONAL DEVELOPMENT IN DROSOPHILA 
Corey S. Goodman, Ph.D., Investigator 
The molecular mechanisms that control how 
neuronal growth cones find and recognize their 
correct targets during development are a focus of 
Dr. Goodman's laboratory. Previous studies have 
shown that neuronal growth cones can navigate 
over long distances and often through a series of 
complex choice points to find their correct targets; 
they appear to do so by following signals on the 
surfaces of cells (both glia and other axons) and in 
the extracellular matrix; evidence from other labo- 
ratories suggests that they can also follow diffusible 
gradients. One major aim is to uncover the adhe- 
sion, recognition, and signaling molecules that im- 
part specificity on the developing nervous system 
and, in so doing, allow grovi^h cones to recognize 
their correct pathways and targets differentially. 
Molecular genetic approaches in Drosophila are 
being used to address these issues. 
I. Mechanisms of Axonal Guidance in Drosophila . 
A. Glial pathways. The midline glia (which originate 
from the mesectoderm), longitudinal glia (which 
originate from a glioblast), and nerve root glia ap- 
pear to provide both permissive substrates for nerve 
outgrowth and some level of instructive information 
for the differential guidance of the initial "pioneer- 
ing" growth cones as they actively choose which glia 
to extend toward and along. When these glial cells 
are eliminated selectively by either laser or genetic 
ablation, specific pathways do not form, leading to 
the conclusion that these early glia play an important 
role in establishing the prepattern for the central 
nervous system (CNS) scaffold and nerve root axon 
pathways. Using the "enhancer trap" method, mem- 
bers of the laboratory have developed a variety of 
molecular lineage markers for these different classes 
of embryonic glia and have identified and cloned 
new genes specifically expressed by these gfia. 
B. Axon pathways. Once the initial axon pathways 
are established, the predominant guidance cue for 
subsequent follower growth cones is the surface of 
the earlier axons in these pathways. Growth cones 
are able to distinguish one axon bundle, or fascicle, 
out of an array of many such pathways within their 
filopodial grasp. The analysis of this phenomenon 
led Dr. Goodman and his colleagues several years 
ago to propose the hypothesis of labeled pathways, 
which predicts that the orthogonal array of com- 
missural, longitudinal, and peripheral nerve root 
pathways are differentially labeled by recognition 
molecules that allow growth cones to navigate 
through these complex choice points. 
II. Molecular Genetics ot Drosophila Adhesion 
Molecules. 
Two different methods have been used to identify 
and clone numerous cell and substrate adhesion 
molecules in Drosophila. In one set of studies, cell 
and substrate adhesion molecules were identified 
that are the homologues of well-known vertebrate 
adhesion molecules (e.g., the three Drosophila 
laminin genes and two different Drosophila 
cadherin genes). In the second set of studies, an 
immunological approach was used to identify and 
clone the genes encoding four different surface gly- 
coproteins: fasciclin I, II, and III and neuroglian. 
These glycoproteins are dynamically expressed on 
different overlapping subsets of axon fascicles and 
glia during embryonic development and are thus 
good candidates for cell adhesion molecules. All 
four of these proteins appear to be homophilic cell 
adhesion molecules. 
Genetic screens are also presently under way to 
identify mutations in new genes involved in path- 
finding and/or synaptic specificity. Because mutants 
in several neural cell adhesion molecules (fasciclin I 
and III) are viable, show no gross CNS defect, but 
do show behavioral phenotypes, members of the 
laboratory have begun screens for behavioral mu- 
tants (using the P element-mediated enhancer trap 
method) to identify genes involved in CNS wiring. 
Dr. Alex Kolodkin has isolated and is genetically 
and phenotypically characterizing several new mu- 
tations that affect flight behavior and are associated 
with p-galactosidase expression in subsets of devel- 
oping neurons. 
A. Laminin. Dr. Denise Montell cloned the genes 
that encode the three subunits of Drosophila 
laminin, a substrate adhesion molecule shown to 
be a potent promoter of neurite outgrowth by pre- 
vious studies on developing vertebrate neurons. Dr. 
Russell Rydel has isolated a lethal mutation in the 
gene encoding the A subunit of laminin {lama). 
This mutation appears to be associated with defects 
in neurite outgrowth and pathfinding in the de- 
veloping peripheral nervous system, defects in 
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