Determination and Maintenance of Cell Type 
Richard H. Gomer, Ph.D. — Assistant Investigator 
Dr. Gomer is also Assistant Professor of Biochemistry and Cell Biology at Rice University and Adjunct 
Assistant Professor of Cell Biology at Baylor College of Medicine. He received his B.A. degree in physics 
from Pomona College and his Ph.D. degree in biology from the California Institute of Technology. He was 
a postdoctoral fellow in the laboratory of Richard Firtel at the University of California, San Diego. 
OUR laboratory is interested in the general 
problem of differentiation and morphogen- 
esis. We are trying to understand at a molecular 
level some of the factors that determine the cell 
type into which an embryonic cell differentiates 
and how the ratios of the different cell types are 
then maintained in an organism. As a model sys- 
tem, we are using the slime mold Dictyostelium 
discoideum. 
Dictyostelium normally exists as undifferen- 
tiated single cells called amoebae that eat bacte- 
ria in soil and decaying leaves and proliferate by 
cell division. When the amoebae eventually over- 
grow their food supply and starve, they aggregate 
together in groups of about 100,000. Roughly 80 
percent of these cells become spores. (A spore is 
a cell with a tough outer coat that forms an 
"escape capsule.") The remaining 20 percent of 
the cells form a stalk about 2 mm high that holds 
the spore cells off the ground. A spore, dispersed 
by the wind, will crack open to release an 
amoeba, which may luckily find itself in the 
midst of a new supply of bacteria. The advantage 
of this organism is its simplicity: cells differen- 
tiate into just two main types. 
Determining Cell Fate 
In the presence of a food source, Dictyoste- 
lium cells grow to a certain size and then separate 
their chromosomes to opposite sides of the cell 
and divide in two. The cycle of growth and divi- 
sion then repeats. In a field of cells, there will be 
cells at all different phases of this cycle. 
Dictyostelium uses a simple and elegant mech- 
anism based on this cycle to determine whether a 
cell will become stalk or spore. When the cells 
starve, those cells that have recently separated 
their chromosomes and divided will become 
stalk cells; the remaining cells will become 
spores. As long as the cells are randomly distrib- 
uted with respect to the phase of their cell cycles, 
there will always be the proper percentage of 
cells in the "stalk" quadrant. We refer to this as a 
musical chairs mechanism, since the decision of 
any given cell to become either stalk or spore is 
made by the phase of the cycle that the cell hap- 
pens to be in at the time of the differentiation 
signal (starvation). 
Cell-type choice determination mechanisms of 
this sort may operate in humans, and aberrations 
could thus lead to birth defects. We are develop- 
ing a variety of techniques that use DNA inserted 
into Dictyostelium cells to identify genes in- 
volved in cell-type differentiation. In the past 
year we have engineered DNA constructs to mu- 
tate Dictyostelium cells three ways: by having 
too many copies of a sequence of DNA, by insen- 
ing foreign DNA into the chromosomal DNA, and 
by making RNA that binds to and renders useless 
the RNA encoding a specific protein. In prelimi- 
nary experiments with these constructs, we have 
identified mutants that may have abnormal ratios 
of the two cell types. In addition, to examine the 
extent of the linkage between the cell cycle and 
cell-type choice, we have treated cells with drugs 
that disrupt the cell cycle. These experiments 
confirmed that the cell-type choice mechanism is 
linked to the cell cycle and does not use a sepa- 
rate timer. 
Sensing Cell Density 
During Dictyostelium development, cells turn 
on the stalk- or spore-specific genes only when 
above a certain cell density. Being able to sense 
whether other cells are nearby represents a para- 
digm for possible mechanisms that would allow, 
for instance, liver cells or others to sense how 
much of the body is composed of liver cells. At 
present, little is known about the molecular 
mechanisms whereby the size and density of a 
tissue are sensed by individual cells. Such mecha- 
nisms would be centrally involved in the regula- 
tion of growth during development, wound heal- 
ing, and regeneration. In addition, an important 
and relevant aspect of tumor cells is that they 
have lost their ability to regulate the size and/or 
density of the tissue and, as a result, proliferate. 
One way this could happen would be if the tumor 
cells could no longer properly sense the total 
mass of the tissue. 
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