Genetic Control of Nematode Development 
process, as a tenth gene functions to prevent the 
action of the nine cell death genes in surviving 
cells. In addition, this regulatory gene is itself 
controlled in a cell-specific fashion by other 
genes that decide which cells are to live and 
which are to die. We are currently analyzing mo- 
lecularly genes involved in programmed cell 
deaths in C. elegans. 
We hope that knowledge of what makes cells 
die and of what can block the cell death process 
in C. elegans will lead to methods that will pre- 
vent the cell deaths responsible for human 
disorders. 
Cell Migration 
During animal development, cells are often 
generated far from their final positions and must 
migrate considerable distances before being able 
to function. To understand what causes cells both 
to migrate and to stop migrating, we are analyzing 
two C. elegans cell migrations. The first involves 
a pair of muscle precursor cells that are born in 
the posterior body region and move to a central 
position along the animal's length, near its gonad. 
We have discovered that these migrations involve 
signaling between the migrating cells and go- 
nadal cells located at the termination site of the 
migration and are now characterizing genes that 
function in this signaling process. 
The second migration we have studied involves 
a pair of neuronal cells that move from the tail 
region to the midbody region of the animal. Thir- 
teen genes have been identified that must func- 
tion for these neuronal migrations to occur prop- 
erly. Some of these genes probably act in the 
migration process per se, but some do not. The 
actions of some of these latter genes allow these 
neurons to acquire their identities; if these genes 
do not function, these neurons fail to express 
their normal characteristics, including their 
long-range cell migration. 
Opposite: The microscopic nematode Czenorhahditis elegans is used to identify and analyze genes 
that control development and behavior. Many of the genes that act in this simple animal are 
strikingly similar to genes found in humans. For example, theC. elegans let-60 gene is very similar 
to human ras genes. Mutations that cause ras genes to be abnormally active are oncogenic and 
constitute the most frequent class of mutation associated with human cancers. 
The figure shows a normal C. elegans adult ( top panel) and two different types o/let-60 mu- 
tants. In the middle animal, the let-60 gene is inactivated, preventing certain cell interactions 
that normally induce formation of a component of the system used for egg laying. The animal is 
filled with retained eggs. By contrast, the lower animal is a mutant in which the let-60 gene is 
abnormally active, leading to the formation of abnormal growths (indicated by arrowheads). 
The study of the C elegans let-60 gene, in providing insights to the function of ras genes, might help 
reveal ways in which ras gene activity and cancerous growth could be inhibited. 
Research of H. Robert Horvitz. Photographs by Gregf. Beitel. 
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