Molecular Genetics of Neuronal Recognition 
in Drosophila 
Corey S. Goodman, Ph.D. — Investigator 
Dr. Goodman is also Class of '33 Professor of Genetics and Neurobiology in the Department of Molecular 
and Cell Biology at the University of California, Berkeley, and Adjunct Professor in the Department of 
Physiology at the University of California, San Francisco. He received his B.S. degree in biology from 
Stanford University and his Ph.D. degree in developmental neurobiology from the University of California, 
Berkeley. His postdoctoral work in developmental neurobiology was done with Nick Spitzer at the Univer- 
sity of California, San Diego. Prior to his present position. Dr. Goodman was a faculty member at Stanford 
University. His honors include the Alan T. Waterman Award from the National Science Board. 
WE are interested in understanding the mo- 
lecular mechanisms by which neuronal 
growth cones find their way toward, and ulti- 
mately recognize, their correct targets during de- 
velopment. Growth cones navigate over long dis- 
tances and often through a series of complex 
choice points, appearing to follow signals on the 
surfaces of cells and in the extracellular environ- 
ment. We would like to uncover the molecules 
that impart specificity to the developing nervous 
system and thus allow growth cones to recognize 
their correct pathways and targets. To address 
these issues, we use molecular genetic ap- 
proaches in the fruit fly Drosophila. 
Our ongoing cellular analysis of the develop- 
ing central nervous system in the insect embryo 
has given rise to five major conclusions: 
First, certain glial and mesectodermal cells ap- 
pear to interact with one another, several under- 
going specific cell migrations, and in so doing lay 
down a pattern for the major fiber pathways in the 
developing nervous system. 
Second, these glial and mesectodermal cells 
provide instructive information for differential 
guidance of the initial, "pioneering" growth 
cones as they choose which cells to extend to- 
ward or along. For example, a specific subset of 
cells at the midline appear to provide an attrac- 
tive cue for the growth cones that extend toward 
the midline and pioneer the commissural axon 
pathways. 
Third, once the pathways are established, the 
predominant guide for "follower" growth cones 
is the surface of the earlier axons in these path- 
ways. Growth cones are able to distinguish one 
particular axon bundle, or fascicle, out of an 
array of many. The experimental analysis of these 
phenomena led to the labeled pathways hypothe- 
sis, which holds that the nerve pathways are dif- 
ferentially labeled by recognition molecules that 
enable growth cones to navigate through com- 
plex choice points. 
Fourth, our observations suggest that the ex- 
pression of surface recognition molecules is dy- 
namic and regional on the surface of individual 
neurons — that parts of the cell are differentially 
labeled in accordance with the processes around 
it for which it has a selective affinity. For exam- 
ple, a neuron might express different molecules 
on the surface of its commissural process as com- 
pared with its longitudinal process, reflecting its 
changing behavior as it navigates across the mid- 
line in a commissural pathway and then turns into 
a different longitudinal pathway. 
Finally, having navigated along a series of path- 
ways, growth cones are capable of recognizing 
their correct target cells. In the Drosophila em- 
bryo, the specificity of neuronal growth cones for 
target cells is most clearly studied in the ability of 
motoneuron growth cones to recognize specific 
muscle fibers. 
Our molecular genetic approach to these is- 
sues has been fourfold. First, we have been study- 
ing in Drosophila the expression and function of 
cell and substrate adhesion molecules that are 
likely to play a significant role in these events. 
For example, we cloned the three genes that en- 
code the three subunits of Drosophila laminin, a 
substrate adhesion molecule previously shown to 
be a potent promoter of neurite outgrowth of de- 
veloping vertebrate neurons. We have isolated a 
lethal mutation in the gene encoding the A sub- 
unit of laminin (lama) and are looking for muta- 
tions in the other two genes. 
We have also cloned two Drosophila genes — 
fat and dachsous — that encode cadherin-like 
molecules (calcium-dependent cell adhesion 
molecules). One class of mutations in the fat 
gene cause a tumor-like overgrowth of epidermal 
tissues. Another class of mutations, as well as a 
class of dachsous mutations, alter the morpho- 
genesis of epidermal tissues. Thus these two 
members of the cadherin gene superfamily are 
involved in the control of morphogenesis; at least 
one of the genes also functions as a tumor sup- 
pressor gene. 
Second, beginning with an immunological ap- 
proach, we identified and cloned the genes en- 
coding four different surface glycoproteins. We 
call these proteins fasciclin I (fas I), fasciclin II 
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