Cell Migration 
Animal development involves cell migrations. To 
understand what causes cells both to migrate and to 
stop migrating, this laboratory has analyzed a num- 
ber of C. elegans cell migrations. One gene that 
controls a specific neuronal migration encodes a 
presumptive transcription factor of the zinc finger 
class, which suggests that this protein specifically 
regulates the expression of genes involved in this 
cell migration. 
Five other genes control the migrations of the two 
sex myoblast (SM) cells, which are born in the poste- 
rior body region and move to a central position 
along the animal's length, near its gonad. These 
genes function within an intercellular signaling sys- 
tem that attracts the migrating SM cells to the gonad. 
At least one of these genes, sem-5, also acts in the 
signal transduction system that functions in the in- 
duction of the C. elegans vulva. 
Cell Differentiation 
Genes involved in the differentiation of both 
nerves and muscles have been identified. Some of 
these genes control the pioneering outgrowth of 
axons along the basement membrane. Other genes 
control neuron-neuron interactions along bundles 
of fasciculated neurons. One of these genes, unc- 
76, appears to encode a novel cytoplasmic protein. 
Other genes affect the acquisition of neuronal iden- 
tity, the onset of neuronal differentiation, neuro- 
transmitter expression, or synaptic function. (These 
studies were supported by a grant from the National 
Institutes of Health.) 
Muscle differentiation has been examined by 
identifying mutants abnormal in muscle structure 
and function. Four genes appear to encode interact- 
ing components of a muscle membrane protein 
complex that regulates muscle contraction. 
Dr. Horvitz is also Professor of Biology at the 
Massachusetts Institute of Technology and Neuro- 
biologist (Neurology) and Geneticist (Medicine) 
at the Massachusetts General Hospital, Boston. 
Books and Chapters of Books 
Brown, R., Jr., and Horvitz, H.R. 1992. Research 
directions in ALS: problems and prospects. In 
Handbook of Amyotrophic Lateral Sclerosis 
(Smith, R.A., Ed.). New York: Dekker, pp 739- 
753. 
Choi, D., Barde, Y., Chalfie, M., Heinemann, U., 
Horvitz, H.R., Kosik, K., Muller, H., Schwarcz, 
R., Schwarz, M., Shooter, E., Siesjo, B., and Un- 
sicker, K. 1991- Neuronal death and survival. In 
Neurodegenerative Disorders: Mechanisms and 
Prospects for Therapy (Price, D.L., Thoenen, H., 
and Aguayo, A.J., Eds.). New York: Wiley, pp 
233-248. 
Horvitz, H.R., and Chalfie, M. 1991. Implications 
of nematode neuronal cell death for human neuro- 
logical disorders. In Neurodegenerative Dis- 
orders: Mechanisms and Prospects for Therapy 
(Price, D.L., Thoenen, H., and Aguayo, A.J., Eds.). 
New York: Wiley, pp 5-19. 
Articles 
Bargmann, C.I., and Horvitz, H.R. 1991- Chemo- 
sensory neurons with overlapping functions di- 
rect chemotaxis to multiple chemicals in C. ele- 
gans. Neuron 1 -.12^-1 AT.. 
Clark, S.G., Stern, M.J., and Horvitz, H.R. 1992. 
C. elegans cell-signalling gene sem-5 encodes a 
protein with SH2 and SH3 domains. Nature 
356:340-344. 
Ellis, R.E., Jacobson, D.M., and Horvitz, H.R. 
1991. Genes required for the engulfment of cell 
corpses during programmed cell death in Caen- 
orhabditis elegans. Genetics 129:79-94. 
Hengartner, M.O., Ellis, R.E., and Horvitz, H.R. 
1992. Caenorhabditis elegans gene ced-9 pro- 
tects cells from programmed cell death. Nature 
356:494-499. 
Horvitz, H.R., and Herskowitz, I. 1992. Mecha- 
nisms of asymmetric cell division: two Bs or not 
two Bs, that is the question. Cell 68:237-255. 
Levin, J.Z., and Horvitz, H.R. 1992. The Caeno- 
rhabditis elegans unc-93 gene encodes a puta- 
tive transmembrane protein that regulates muscle 
contraction . / Cell Biol 117:143-155. 
Li, P.M., Reichert, J., Freyd, G., Horvitz, H.R., and 
Walsh, C.T. 1991. The LIM region of a presump- 
tive Caenorhabditis elegans transcription factor 
is an iron-sulfur- and zinc-containing metallodo- 
main. Proc Natl Acad Sci USA 88:9210-9213- 
Mclmire, S.L., Garriga, G., White, J., Jacobson, D., 
and Horvitz, H.R. 1992. Genes necessary for di- 
rected axonal elongation and fasciculation in C. 
elegans. Neuron 8:307-322. 
Stern, M.J., and Horvitz, H.R. 1991. A normally 
attractive cell interaction is repulsive in two C. 
elegans mesodermal cell migration mutants. De- 
velopment 113:797-803. 
Sternberg, P.W., and Horvitz, H.R. 1991 Signal 
transduction during C. elegans vulval induction. 
Trends Genet 7:366-371. 
NEUROSCIENCE 403 
