quenced tryptic peptides, and used degenerate oli- 
gonucleotides to isolate a CMF gene. Bacterially syn- 
thesized CMF has CMF activity, and like the 
breakdown peptides, specific bacterially synthe- 
sized CMF fragments have even higher activity. This 
indicates that the cloned cDNA encodes CMF. Using 
antibodies directed against bacterially synthesized 
CMF, Dr. Comer's laboratory has found that CMF is 
present in approximately the same amount in all 
Dictyostelium cells and is secreted by both prestalk 
and prespore cells. Diffusion calculations based on 
the canonical secretion showed that an isolated 
starved cell does not secrete enough CMF to trigger 
itself, whereas a high density of starved cells will 
stimulate themselves. 
At the same time that cells are sensing CMF, they 
begin to use pulses of cAMP as a chemoattractant for 
aggregation. CMF is required for this cAMP pulse- 
mediated aggregation. In collaboration with Dr. 
Peter Van Haastert at the University of Groningen 
(the Netherlands), Dr. Comer's laboratory has 
found that CMF does not affect the binding of cAMP 
to cell-surface cAMP receptors but does interfere 
with the ability of the receptors to activate via G 
proteins two enzymes: adenylate cyclase and guany- 
late cyclase. These results are helping to explain 
how CMF allows Dictyostelium cells to sense their 
relative density. The CMF project was supported by 
a grant from the National Institutes of Health. 
Dr. Gomer is also Assistant Professor of Bio- 
chemistry and Cell Biology at Rice University and 
Adjunct Assistant Professor of Cell Biology at Bay- 
lor College of Medicine. 
Articles 
Clarke, M., Dominguez, N., Yuen, I.S., and Gomer, 
R.H. 1992. Growing and starving Dictyostelium 
cells produce distinct density-sensing factors. 
Dev Biol 152:403-406. 
Jain, R., Gomer, R.H., and Murtagh, J.J., Jr. 1992. 
Increasing specificity from the PCR-RACE tech- 
nique. Biotechniques 12:58-59. 
Jain, R., Yuen, I.S., Taphouse, C.R., and Gomer, 
R.H. 1992. A density-sensing factor controls de- 
velopment in Dictyostelium. Genes Dev 6:390- 
400. 
Yuen, I.S., Taphouse, C, Halfant, K., and Gomer, 
R.H. 1991. Regulation and processing of a se- 
creted protein that mediates sensing of cell den- 
sity in Dictyostelium. Development 113:1375- 
1385. 
DEVELOPMENTAL CONTROL OF GENE EXPRESSION 
Rudolf Grosschedl, Ph.D., Assistant Investigator 
The process of terminal differentiation turns a 
multipotential cell into a cell that carries out a par- 
ticular function or synthesizes a specific product. 
The lymphoid B cell lineage ultimately generates a 
cell that secretes antibody. During B cell differentia- 
tion, several genes are expressed in a defined cell- 
type-specific and temporally ordered pattern. 
Transcription of the fi immunoglobulin gene en- 
coding the heavy chain (IgH) of the antibody can be 
detected in virtually all lymphocytes. By contrast, 
the K gene encoding the light chain of the antibody 
is transcribed only in late-stage B cells, and the mb- 1 
gene encoding an antibody-associated protein is ex- 
pressed only in early-stage B cells. The goal of Dr. 
Grosschedl's research is to gain some insight into 
the molecular mechanisms that mediate the de- 
velopmental control of lymphoid-specific gene 
expression. 
Tissue-Specific and Temporal Regulation 
of Ig Gene Expression in a Transgenic Model 
The Ig genes represent one of the best-studied 
paradigms for cell-type-specific gene expression. 
Efforts by many laboratories to dissect the regulation 
of Ig genes in cell culture and in vitro allowed for 
the identification and characterization of several 
cis- and trans-acting regulatory components. These 
studies, which were attempts to reduce the com- 
plexity of regulation, provided a detailed insight 
into the properties of individual components. How- 
ever, they did not indicate how these components 
are integrated to generate the developmental pat- 
tern of ji gene expression observed in vivo. There- 
fore Dr. Grosschedl and his colleagues adopted gene 
transfer into the mouse germline to examine the 
contribution of various cis-acting sequences to the 
regulation of an intact rearranged gene in vivo. Spe- 
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