bute is consistent with the presence of sequence 
motifs previously associated with nuclear functions. 
The existence of more than a single TLE and Notch 
gene suggests that structural redundancy may be a 
feature of the human counterparts of the develop- 
mentally important genes of the Drosophila Notch 
group. 
The extraordinary' structural conservation among 
the Drosophila and human gene products implies 
that the biochemical mechanisms involving Notch 
and Enhancer of split may also be conserved across 
species boundaries. However, the identification of 
multigene families suggests that gene duplication 
events have created a more complex situation in 
mammals. If the Notch group role has been con- 
served from flies to vertebrates, then a general and 
pleiotropic pathway involved in controlling many 
aspects of mammalian cell fate may have been 
identified. 
Dr. Artavanis-Tsakonas is also Professor of Cell 
Biology and Biology at the Boyer Center for Mo- 
lecular Medicine at Yale University School of 
Medicine. 
Articles 
Artavanis-Tsakonas, S., and Simpson, P. 1991. 
Choosing a cell fate: a view from the Notch locus. 
Trends Genet 7:405-408. 
Rebay, I., Fleming, R.J., Fehon, R.G., Cherbas, L., 
Cherbas, P., and Artavanis-Tsakonas, S. 1991. 
Specific EGF repeats of Notch mediate interac- 
tions with Delta and Serrate: implications for 
Notch as a multifunctional receptor. Cell 
67:687-699. 
Xu, T., Caron, L.G., Fehon, R.G., and Artavanis- 
Tsakonas, S. 1992. The involvement of the 
Notch locus in Drosophila oogenesis. Develop- 
ment 115.915-922. 
THE MOLECULAR BIOLOGY OF SMELL: GENES ENCODING RECEPTORS 
AND CHANNELS IN THE NOSE 
Richard Axel, M.D., Investigator 
Environmental stimuli are recognized by sensory 
neurons, and this information is transmitted to the 
brain, where it is decoded to provide an internal 
representation of the external world. The olfactory- 
sensory system of vertebrates can recognize and dis- 
criminate a large number of odorants of diverse mo- 
lecular structure. For example, humans are capable 
of distinguishing thousands of distinct odors. Al- 
though odorants often exhibit widely different 
structures, subtle changes in molecular structure 
can lead to striking differences in perceived odor. 
How do olfactor}' sensory neurons recognize the 
vast array of molecular structures that are defined as 
odorants? The detection of distinct odorants presum- 
ably results from the association of odorous ligands 
with specific receptors on olfactory neurons. Dis- 
crimination among distinct odors will then require 
that the brain distinguish which receptors have 
been activated. 
In initial experiments to define the logic underly- 
ing olfactory perception. Dr. Axel and Dr. Linda 
Buck identified and cloned a large family of genes 
that are likely to encode odorant receptors in the rat. 
This multigene family encodes seven transmem- 
brane domain receptors and belongs to the super- 
family of G protein-coupled receptors. The size of 
the gene family in mammals (perhaps as large as 
1,000 genes) suggests that olfactory perception em- 
ploys a large number of receptors, each capable of 
interacting with one or a small number of odorous 
ligands. The interaction of odorous ligands with a 
large number of receptors on olfactory^ sensory neu- 
rons provides a mechanism for the specific recogni- 
tion of a diverse array of odors. 
Isolation and Sequence of Catfish Olfactory 
Receptor cDNAs 
In subsequent experiments to discern the mecha- 
nism of processing of olfactory information. Dr. 
Axel and his colleagues have asked whether cells 
expressing a specific odorant receptor (and there- 
fore responsive to specific odors) are spatially segre- 
gated in the olfactory^ epithelium. The channel cat- 
fish was chosen as a model system for two major 
reasons: first, the repertoire of putative odorant re- 
ceptors is numerically far simpler than in mammals, 
and second, the catfish olfactory- epithelium is orga- 
nized in a simple, regularly repeating anatomic 
structure. It is therefore possible to examine the 
patterns of receptor expression of a significant frac- 
tion of the repertoire with a relatively small number 
of receptor probes. 
The isolation of cDNA clones encoding putative 
olfactory- receptors from catfish sensory- neurons was 
392 
