address these issues. Based on their increasing 
knowledge of the cell biology and the availability of 
specific probes, this laboratory has undertaken a se- 
ries of large-scale, systematic mutant screens in 
order to identify genes that control growth cone 
guidance and target recognition in the Drosophila 
embryo. Over the past year, many new genes have 
been identified, including genes that 1) control the 
guidance of growth cones either toward or away 
from the midline either to enter or avoid the com- 
missures of the central nervous system, 2) control 
the guidance of growth cones along longitudinal 
axon pathways of the central nervous system, and 3) 
control the ability of motoneuron growth cones to 
find and recognize their appropriate target muscles. 
Many of these genes are likely to encode important 
components of mechanisms that impart specificity 
on the events of pathway and target recognition. 
Several of these new genes, including commis- 
sureless and roundabout, are under molecular 
investigation. 
The developing Drosophila retina provides one 
of the few systems where the molecular mechanisms 
of short-range inductive interactions can be studied 
at the level of individual cells. The fate of a cell 
within the retina appears to be governed by the spe- 
cific combination of signals received by that cell 
from its immediate neighbors. Research in the labo- 
ratory of Investigator Gerald M. Rubin, Ph.D. (Uni- 
versity of California, Berkeley) is aimed at gaining 
an understanding of how such signals are generated, 
sensed, and responded to by cells in the developing 
retina. During the past year the laboratory has used a 
novel genetic approach to identify several of the 
components that act downstream of a transmem- 
brane protein-tyrosine kinase receptor that trans- 
duces a signal essential for the determination of one 
particular photoreceptor cell type. 
Associate Investigator S. Lawrence Zipursky, 
Ph.D. (University of California, Los Angeles) and his 
colleagues also have been studying visual system de- 
velopment in the fruit fly. This model has allowed 
them to address several fundamental questions in 
development. How do cells communicate during de- 
velopment to regulate that the right cell forms in the 
right place? What mechanisms control the rate of 
cellular proliferation? And finally, how do neurons 
form precisely arranged networks of interconnected 
cells? Through the molecular and developmental 
analysis of mutants defective in visual system devel- 
opment, this laboratory has gained insight into the 
molecular mechanisms underlying some of these 
processes. 
The overall objective of the research of Assistant 
Investigator Hermann Steller, Ph.D. (Massachusetts 
Institute of Technology) and his colleagues is to un- 
derstand how functional neuronal circuits are estab- 
lished and maintained during development. Their 
efforts also are focused primarily on visual system 
development in Drosophila, where these processes 
can be studied at the level of individual cell types. 
They have isolated mutations that afi'ect the genera- 
tion of specific neurons, the formation of proper 
neuronal connections, and the elimination of cells 
through programmed cell death. Genes correspond- 
ing to some of these mutants have been cloned and 
are being analyzed. 
The main goal of the laboratory of Associate Inves- 
tigator Charles S. Zuker, Ph.D. (University of Califor- 
nia, San Diego) is to elucidate mechanisms used for 
signal transduction in sensory systems. In particular, 
the work focuses on a molecular genetic dissection 
of visual transduction and mechanotransduction. 
Several molecules playing critical roles in the in 
vivo regulation of the phototransduction cascade 
process have been characterized and include 
members of the family of immunosuppressing bind- 
ing proteins, two arrestin homologues, and enzymes 
involved in metabolism of the intracellular messen- 
ger inositol trisphospate. Work on mechanorecep- 
tors is aimed at understanding how the mechanical 
senses — for instance, touch, hearing, and balance 
— work at a molecular level. Drosophila bears an 
abundance of mechanosensory organs, some of 
which show physiological similarities to mechano- 
receptors in the vertebrate inner ear. The laboratory 
has isolated several mutations that aifect the devel- 
opment or gross structure of the Drosophila exter- 
nal adult mechanosensory organs and some in which 
the organs are all present and properly formed but 
may have abnormal physiology. 
Research of the laboratory of Associate 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 cell and body patterns in Dro- 
sophila. Several potential signaling molecules have 
been identified and their functions assessed by alter- 
ing their structures or patterns of expression. These 
studies have established that most aspects of antero- 
posterior body pattern are specified in early em- 
bryos by the graded distributions of two transcrip- 
tion factors, bicoid and hunchback protein. They 
have also implicated the secreted wingless protein 
as a morphogen controlling dorsoventral pattern in 
the developing limbs. 
NEUROSCIENCE 383 
