Hox-1.8, which is expressed early in kidney devel- 
opment and may thus be important in this process, 
has been found. 
The laboratory of Assistant Investigator Ruth Leh- 
mann, Ph.D. (Massachusetts Institute of Technol- 
ogy) explores development in the fruit fly. Essential 
clues for the establishment of the Drosophila body 
plan are provided to the egg cell during its matura- 
tion in the mother fly, and these signals are under 
study. Some of the maternal gene products are local- 
ized to specific egg regions. At the posterior pole, 
signals required for the formation of the embryonic 
abdomen and for the determination of germ cells are 
stored in the form of RNA. Mislocalization of these 
RNA molecules to new positions within the egg cell 
can be achieved by exchange of RNA localization 
signals. Such experiments show that mislocalization 
of nanos RNA is sufficient to induce a second abdo- 
men in the fly and that mislocalization of 05^ar RNA 
induces germ cell formation. 
Research of Assistant Investigator Sean B. Carroll, 
Ph.D. (University of Wisconsin) and his colleagues 
is also focused on groups of genes that govern the 
formation of body structures in Drosophila and in 
other insects as well, with the goal of understanding 
how body patterns are created and how they evolve. 
In the past year they have identified several compo- 
nents of a genetic hierarchy that guides the forma- 
tion of the entire Drosophila wing. The wingless 
protein, one member of a gene family involved in 
the large-scale patterning of various invertebrate 
and vertebrate structures, appears to be the earliest 
activity product that regulates the spatial expression 
of the dorsal-specific apterous gene and the wing- 
specific vestigial and scalloped genes. In a separate 
comparative study of many fly species, this labora- 
tory has determined that the molecular regulatory 
mechanisms guiding pattern formation in these ani- 
mals are highly conserved and functionally inter- 
changeable, even after 40-80 million years of evo- 
lutionary divergence. 
The laboratory of Investigator Allan C. Spradling, 
Ph.D. (Carnegie Institution) examines the role 
played by changes in genome structure during the 
development of the fruit fly. Heterochromatic chro- 
mosome regions that contain one-quarter of the Dro- 
sophila DNA sequences are panially lost during the 
normal development of many somatic cells, includ- 
ing the ovarian nurse cells. It is not known if these 
dramatic alterations are functionally important. This 
group is studying the relationship of genomic alter- 
ations to the functioning and regulation of stem 
cells and nurse cells during oogenesis. A largely 
heterochromatic minichromosome and several 
genes that disrupt these aspects of oogenesis pro- 
vide the necessary tools. 
Investigator David H. Beach, Ph.D. (Cold Spring 
Harbor Laboratory) and his colleagues focus on the 
regulation of the cell division cycle in model organ- 
isms such as yeast, but also in mammalian cells. The 
division cycle of all eukaryotic cells is controlled by 
a mitotic oscillator that consists of a family of 
closely related protein kinases. Each kinase has a 
catalytic subunit and a cyclin regulatory subunit. 
The group is investigating the cyclin kinases and at- 
tempting to understand how their function is inte- 
grated into the signal transduction pathway that reg- 
ulates mitogenesis. 
Cells respond to growth regulatory factors only 
during the G, phase of their division cycle, when 
they prepare to duplicate their chromosomes. How- 
ever, once DNA replication begins, growth factors 
are no longer necessary to ensure subsequent steps 
in cell division. Colony-stimulating factor 1 (CSF-1) 
induces cell proliferation by binding to specific cell 
surface receptors which, in turn, generate intracel- 
lular signals that govern gene expression. These sig- 
nals are under study by the laboratory of Investigator 
CharlesJ. Sherr, M.D., Ph.D. (St. Jude Children's Re- 
search Hospital). Targets of the signaling pathways 
have been found to include novel Gj cyclin genes 
that may control the cell's commitment to DNA syn- 
thesis. Genetic changes that perturb either CSF-1- 
induced signal transduction or cyclin gene expres- 
sion can contribute to the development of cancer. 
In a cell cycle, DNA is first faithfully replicated 
(S phase) and then distributed to daughter cells at 
mitosis (M phase). Cells have an elaborate check- 
point before mitosis (in G2 phase) to make sure all 
DNA is fully replicated before initiating mitosis by 
activation of cdc2 kinase, and this is under study by 
Investigator James L. Mailer, Ph.D. (University of 
Colorado) and his colleagues. The cdc25 phospha- 
tase activates cdc2 only after phosphorylation of the 
phosphatase itself. Increased phosphorylation is in 
part a consequence of decreased phosphatase activ- 
ity against cdc25 itself. A specialized form of cdc2 
known as cdk2 is required for metaphase arrest at 
meiosis II in the unfertilized egg and appears to co- 
operate with the c-mos"^^ proto-oncogene kinase to 
execute this function. Interactions between proto- 
oncogenes and cell cycle control elements are likely 
to be important in the aberrant cell cycles of cancer 
cells. 
The proliferation of cells is controlled by a bal- 
ance of positive and negative signals. The system 
that conveys growth inhibitory signals is similar in 
design to that which signals cell growth. Both in- 
CEIX BIOLOGY AND REGULATION 
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