tion. At later stages the floor plate guides develop- 
ing axons in the embryonic spinal cord, in part by 
releasing a diffusible chemoattractant factor and in 
part by virtue of its speciali2ed cell surface proper- 
ties. There are marked changes in the expression of 
glycoproteins on the surface of axons as they pass 
through the floor plate. To study the regulation of 
these axonal glycoproteins, cDNA clones encoding 
a recently discovered protein of this type, TAG-1, 
have been isolated. TAG-1 belongs to the immuno- 
globulin gene family and may be involved in cell 
recognition and axonal pathfinding in the develop- 
ing central nervous system. 
A major aim of the laboratory of Investigator 
Corey S. Goodman, Ph.D. (University of California 
at Berkeley) is to understand the molecular mecha- 
nisms that control how neuronal growth cones find 
and recognize their correct targets during develop- 
ment. Neuronal growth cones can navigate over 
long distances by following signals on the surfaces 
of cells (both glia and other neurons) and in the ex- 
tracellular matrix. The major aim of this work is to 
uncover the adhesion, recognition, and signaling 
molecules that impart specificity to the developing 
nervous system and in so doing allow growth cones 
to recognize differentially their correct pathways 
and targets. Molecular genetic and classical genetic 
approaches are used to study the function of these 
molecules in the fruit fly, Drosophila melanogaster. 
Over the past year a number of Drosophila neural 
adhesion molecules have been cloned, and a de- 
tailed analysis of their function is under way. 
Assistant Investigator Flora Katz, Ph.D. (Univer- 
sity of Texas Southwestern Medical Center at Dal- 
las) and her colleagues are interested in the mecha- 
nisms by which cell surface interactions in the 
nervous system govern diffierentiation and the es- 
tablishment of neural networks. They have been 
studying a neural-specific cell surface carbohydrate 
modification found on many membrane proteins in 
Drosophila. Extreme disruptions of development 
occur at the nonpermissive temperature in a cold- 
sensitive mutant [nac (neurally altered carbohy- 
drate)] in which this modification is absent. It is 
hoped that study of the biochemistry, molecular bi- 
ology, and cellular and organismal phenotypes of 
this mutant will contribute to an understanding of 
the role of tissue-specific glycosylation in devel- 
opment. 
Research in the laboratory of Investigator Gerald 
M. Rubin, Ph.D. (University of California at Berke- 
ley) is directed toward examination of differentia- 
tion and gene regulation in the developing nervous 
system by studying certain genes whose mutation 
disrupts neural development. During the past year 
Dr. Rubin and his colleagues have focused on sev- 
eral genes important for the determination of cell 
fates in the developing retina of Drosophila. 
Among these are genes encoding cell surface recep- 
tors with structures similar to the mammalian in- 
sulin and epidermal growth factor receptors, and 
regulatory proteins that resemble mammalian DNA- 
binding proteins. Their observations suggest a strik- 
ing evolutionary conservation of basic developmen- 
tal mechanisms from flies to humans. 
Associate Investigator Stephen J. Smith, Ph.D. 
(Yale University) and his colleagues are studying the 
development and function of synaptic connections. 
They are especially concerned with the basic motil- 
ity mechanisms that enable growing nerve fibers to 
locate their proper targets for synapse formation. 
Other projects have led to the collection of video 
sequences of developmental events within intact 
mammalian brain tissue. These new observations 
concern mechanisms of neuronal migration and 
synapse formation during embryonic brain develop- 
ment. Still other projects address the detailed dy- 
namics of intracellular signaling underlying the reg- 
ulation of synaptic development and function. 
Physical growth and retraction of nerve terminals 
cause changes in the circuitry of the brain. Devel- 
opment, repair, and memory depend on this plas- 
ticity. One neuronal protein implicated by several 
laboratories in this process is GAP-43. Associate In- 
vestigator Mark C. Fishman, M.D. (Massachusetts 
General Hospital) and his colleagues have investi- 
gated how GAP-43 is transported through the cell 
to discrete regions of the membrane. GAP-43 was 
found to contain a short stretch of amino acids that 
guides it to specific sites, including the nerve termi- 
nal. Once there it apparently enhances the exten- 
sion of filopodia— long, fine processes from the cell 
surface— that normally characterize growing nerve 
terminals. GAP-43 appears also to interact with 
other proteins at the membrane, some of which are 
known to be important for the transduction of in- 
formation from the cell surface into intracellular 
messages. These other proteins are being isolated 
to see how they mediate a linkage between cell sur- 
face signals and cell shape changes. Finally, a brain- 
specific protein has been identified and cloned that 
binds to the regulatory region of the GAP-43 gene. 
Potassium channels are a diverse group of ion 
channels that are widely distributed in animal and 
plant cells and serve many different functions, in- 
cluding, possibly, learning and memory. The first 
Continued 
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