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MOLECULAR GENETICS OF NEMATODE DEVELOPMENT AND BEHAVIOR 
PaulW. Sternberg, Ph.D., Associate Investigator 
Dr. Sternberg's laboratory takes a molecular genet- 
ics approach to study basic questions in devel- 
opmental biology and neurogenetics, using the 
nematode Caenorhabditis elegans. Cell-type speci- 
fication by intercellular signaling, the genetic con- 
trol of innate behavior, and the genetic and cellular 
basis for morphogenesis are among the problems 
studied. The development and function of the C. 
elegans male copulatory spicules and hermaphro- 
dite vulva provide an opportunity to study these 
problems. The major strategy is to identify muta- 
tions that make cells or animals misbehave and then 
to study the functions of the genes defined by these 
mutations, using a combination of molecular biol- 
ogy and genetic analysis. 
Male Spicule Development 
The concerted morphogenesis of specialized epi- 
dermal cells and neural cells forms the two copula- 
tory spicules, innervated structures crucial to male 
mating with hermaphrodites. Because C. elegans 
hermaphrodites are internally self-fertilizing — each 
animal producing both sperm and ova — male mat- 
ing is evidently a dispensable behavior and the spic- 
ule a dispensable organ. Each of the two spicules 
comprises nine cells: two sensory neurons, one mo- 
toneuron, and six supporting cells, some of which 
secrete a hardened cuticle. 
A number of mutations that disrupt various 
aspects of spicule development have been identi- 
fied. Several mutations are defective in the genera- 
tion of spicule cells, while others affect the differ- 
entiation of the cells and the morphogenesis of 
the spicules. These mutations are being analyzed 
to define a genetic pathway specifying spicule 
development. 
By cell ablation experiments, a network of five or 
more cell interactions crucial to spicule develop- 
ment has been identified. At an intermediate stage of 
spicule development, eight cells are arranged in 
two tiers of four cells each. The dorsal tier is in- 
duced by a signal from the nearby F and U cells. The 
ventral tier receives a signal from the Y.p neuroec- 
toblast or its progeny. In addition, there are three or 
more interactions between the ventral and dorsal 
tiers and within each tier. 
The /m-3, let-23, let-60, and lin-45 genes are nec- 
essary for the induction of the dorsal tier by the cells 
F and U. The lin-3 gene encodes an epidermal 
growth factor (EOF) -like growth factor precursor. 
The let- 2 3 gene encodes a tyrosine kinase of the 
EGF-receptor subfamily. The let-60 gene encodes a 
ras protein. The lin-45 gene encodes a m/ serine- 
threonine protein kinase. Specification of these 
neuroectoblasts thus involves a highly conserved 
signal transduction mechanism. By screening for 
mutants with defective spicules. Dr. Sternberg and 
his colleagues have identified new mutations that 
affect spicule development. 
Mating Behavior 
Male mating, the most complex nematode behav- 
ior, is being studied by cell ablation experiments 
and genetic analysis. A series of steps has been iden- 
266 
