phores, the cells that many animals use to change 
their color rapidly. The bioassay will be useful for 
examining how ligands stimulate or block seven- 
transmembrane domain receptors. 
Analyses of steroid receptors are important for un- 
derstanding molecular details of transcriptional 
control, as well as providing insight as to how an 
individual trans-acting factor contributes to cell 
identity and function. Recent work from the labora- 
tory of Investigator Ronald M. Evans, Ph.D. (Salk In- 
stitute) points to the existence of a specific molecu- 
lar mechanism in the form of a physiologic code 
built into DNA that provides a direct structural corre- 
late to the distinct hormonal signaling pathways for 
retinoic acid, vitamin D, and thyroid hormones. Al- 
though molecular biologic techniques have led to 
the discovery of new receptors, these discoveries, in 
turn, have enabled the identification of novel li- 
gands for these receptors, as exemplified by the re- 
cent characterization by this laboratory of the new 
mammalian hormone 9-cis retinoic acid. It is be- 
lieved that this may be a major physiologic regulator 
in the embryo and the adult and has recently been 
shown to have promise for the treatment of human 
acute promyelocytic leukemia. 
Understanding the molecular mechanisms by 
which the neuroendocrine system develops and by 
which neuropeptides and hormones control critical 
regulatory events is the central goal in the laboratory 
of Investigator Michael G. Rosenfeld, M.D. (Univer- 
sity of California, San Diego). Synergistic interac- 
tions required to produce the precisely restricted 
patterns of cell-specific expression have been iden- 
tified for several pituitary genes. The cloning of 
DNAs complementary to the mRNAs that encode 
pituitary-specific transcriptional activators has pro- 
vided new insights into organogenesis and charac- 
terized novel classes of transcriptional activators. A 
large number of structurally related members of this 
gene family have been identified in the brain and 
exhibit precise temporal and spatial patterns of ex- 
pression in the developing nervous system. Detailed 
structure-function analysis of several hormone re- 
ceptors has provided specific insights into the mo- 
lecular mechanisms of receptor-mediated activation 
of gene expression. 
The nervous system contains a diverse group of 
cells. What tells a cell to become a neuron? How 
does each neuron acquire its own unique identity? 
In the past few years the research group of Investiga- 
tor Yuh Nung Jan, Ph.D. (University of California, 
San Francisco) and other laboratories have identi- 
fied more than 20 genes that appear to have impor- 
tant roles in neurogenesis or in specifying neuronal 
identity. During the past year. Dr. Jan's group has 
studied several of these genes in detail: asense, big 
brain, cut, daughterless, deadpan, neuralized, 
numb, prospero, and rhomboid. All have now been 
cloned. These studies are revealing clues as to how 
these genes affect neural development at the molec- 
ular level, as well as unexpected links between dif- 
ferent developmental processes. 
Taking a primarily genetic approach to answer 
the question of how genes control animal develop- 
ment, members of the laboratory of Investigator H. 
Robert Horvitz, Ph.D. (Massachusetts Institute of 
Technology) have isolated developmental mutants 
of the nematode Caenorhabditis elegans and have 
characterized them using both genetic and molecu- 
lar techniques. Because both the complete cell- 
ular anatomy (including the full wiring diagram 
of the nervous system) and the complete cell lin- 
eage of this nematode are known, mutant animals 
can be studied at the level of single cells, and even 
single synapses. In this way, genes involved in cell 
lineage, cell signaling, cell death, cell migration, 
and cell differentiation have been identified and 
analyzed. 
The so-called "Notch group" of genes has been 
implicated in the general mechanism that is crucial 
for correct developmental choices in a wide variety 
of precursor cells in Drosophila and is under study 
by Investigator Spyridon Artavanis-Tsakonas, Ph.D. 
(Yale University) and his colleagues. The accumu- 
lated genetic and molecular studies suggest that 
these genes encode elements of a cell communica- 
tion mechanism that includes cell surface, cytoplas- 
mic, and nuclear components. The central player of 
the Notch group is the Notch (N) locus, which en- 
codes a transmembrane protein containing EGF-like 
(epidermal growth factor-like) repeats in its extra- 
cellular domain. Evidence suggests that this protein 
may act as a multifunctional receptor, which inter- 
acts molecularly and genetically with two other 
transmembrane, EGF-containing proteins of the 
Notch group: Serrate and Delta. The other known 
members of the Notch group are deltex, Enhancer 
of split, and mastermind. The deltex gtne seems to 
code for a cytoplasmic protein, while mastermind 
and Enhancer of split encode nuclear proteins. Re- 
cent evidence indicates that at least some members 
of the Notch group are present in the human 
genome and may also be involved in cell fate 
decisions. 
The molecular mechanisms that control how neu- 
ronal growth cones find and recognize their correct 
targets during development continue to be the focus 
of Investigator Corey S. Goodman, Ph.D. (University 
of California, Berkeley) and his colleagues. Molecu- 
lar genetic approaches in Drosophila are used to 
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