potassium channel gene (Shaker) has been cloned 
in the laboratory of Investigator Lily Y Jan, Ph.D. 
(University of California at San Francisco) from Z)ro- 
sophila. The strong conservation of potassium 
channel structure has allowed the subsequent iso- 
lation of mammalian potassium channel genes. 
Current studies reveal that one gene in Drosophila 
may give rise to multiple subtypes of potassium 
channels by alternative splicing. Structural compo- 
nents important for specific aspects of potassium 
channel function have also been identified by site- 
directed mutagenesis experiments. 
Work in the laboratory of Investigator Paul R. 
Adams, Ph.D. (State University of New York at Stony 
Brook) focuses on the electrical properties of verte- 
brate nerve cells. The research addresses three 
main issues: What voltage -dependent channels are 
present? How are these channels regulated by 
membrane potential, intracellular calcium, and 
neurotransmitters? What roles do these channels 
play in cell physiology? This work is being pursued 
using several different types of nerve cells: bullfrog 
sympathetic ganglion cells, hippocampal pyramidal 
cells, lateral geniculate cells, and a clonal cell line. 
The laboratory of Associate Investigator Robert 
G. Johnson, Jr., M.D., Ph.D. (University of Pennsyl- 
vania) is interested in the application of sensitive, 
rapid, and noninvasive biophysical techniques to 
study the cellular and molecular regulation of mol- 
ecules within biological membranes that regulate 
the distribution of ions and chemical messengers 
across the plasma and intracellular membranes, 
specifically the Na"*^ pump, nicotinic acetylcholine 
receptor, and a voltage-dependent calcium channel 
in secretory neuroendocrine cells. During the past 
year the laboratory has applied nuclear magnetic 
resonance spectroscopy to the study of the cellular 
regulation of the Na"*^ pump and found that it is 
possible to measure simultaneously the ATPase ac- 
tivity and transmembrane Na^ distribution. Using 
this technique and observing these parameters 
under resting and stimulated conditions. Dr. John- 
son and his colleagues have shown that the activity 
of the Na^ pump in an excitable cell can increase 
dramatically by a mechanism that is independent of 
the intracellular sodium concentration. 
How do genes control animal development? Tak- 
ing a primarily genetic approach to answer this 
question. Investigator H. Robert Horvitz, Ph.D. 
(Massachusetts Institute of Technology) and his col- 
leagues have isolated developmental mutants of the 
nematode Caenorhabditis elegans and have used 
both genetic and molecular genetic techniques to 
characterize these mutants. Because both the com- 
plete cellular anatomy (including the complete wir- 
ing diagram of the nervous system) and the com- 
plete cell lineage of C. elegans are known, mutant 
animals can be studied at the level of single cells 
and even single synapses. In this way, genes in- 
volved in cell lineage, cell death, cell migration, and 
cell differentiation have been identified and ana- 
lyzed. 
Research in the laboratory of Assistant Investiga- 
tor Gary Struhl, Ph.D. (Columbia University) is di- 
rected toward determining the molecular nature 
and mode of action of spatial information responsi- 
ble for organizing the embryonic body plan of Dro- 
sophila. Genes encoding several molecules that be- 
have as spatial cues have been identified and their 
functions assessed by a variety of approaches. 
These studies have recently led to the demonstra- 
tion that different strategies are used to dictate how 
the anterior and posterior halves of the body de- 
velop: the anterior half depends on a single gradi- 
ent morphogen, bicoid, which functions as a con- 
centration-dependent transcriptional activator, 
while the posterior half depends on a number of 
local gradients that arise in response to the polar- 
ized activities of bicoid and two other primary 
morphogens, nanos and torso. 
The nervous system consists of an enormous 
number of different cell types, and one of the cen- 
tral issues in neuroscience is how each neuron ac- 
quires its distinctive identity. In the past few years 
the laboratory of Investigator Yuh Nung Jan, Ph.D. 
(University of California at San Francisco) has iden- 
tified in Drosophila more than 20 genes that bear 
the question of the specification of neuronal iden- 
tity. During the past year the group has studied in 
detail the genes neuralized, big brain, daughter- 
less, cut, cyclin A, rhomboid, and numb. All have 
now been cloned, most by this group. The studies 
are revealing clues as to how these genes affect 
neural development at the molecular level. 
Investigator Louis F. Reichardt, Ph.D. (University 
of California at San Francisco) and his colleagues 
are investigating some of the molecules in the ex- 
tracellular environment that regulate the survival 
and development of neurons in vivo. Among these 
are trophic factors that play a key role in neuronal 
survival. These are proteins that are made in mi- 
nute amounts by cells; to date the best understood 
is nerve growth factor, which regulates the survival 
and differentiation of several neuronal populations, 
including a population of acetylcholine-secreting 
neurons in the brain that are important in cogni- 
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