In vertebrates,
the olfactory epithelium consists of thousands of similar
types of sensory neurons, each uniquely identified by
its sensory properties. This olfactory specificity is
partly mediated by the expression of specific olfactory
receptors in each neuron. I am interested in understanding
the process by which each olfactory neuron acquires and
regulates its characteristic properties.
The nematode
C. elegans provides an excellent model system in
which to study the development and function of chemosensory
neurons. Worms respond to a large number of chemicals
using approximately 32 chemosensory neurons. The functions
of many of these chemosensory neurons have been defined
by laser ablation experiments and mutants with defects
in chemosensory responses have been identified. Several
genes defined by these mutations have been cloned.
Using a behavioral
screen, we identified a gene odr-7, that encodes
a member of the nuclear receptor family of transcriptional
regulators (1). odr-7 is expressed only in the
AWA olfactory neurons. In odr-7 mutants, the AWA
neurons develop normally but lack all sensory function.
Thus odr-7 may regulate the expression of signaling
molecules that provide AWA with its unique sensory profile.
We have recently
shown that a target of odr-7 regulation is the
gene odr-10 (2). odr-10 encodes a seven
transmembrane domain receptor for the volatile odorant
diacetyl, sensed by the AWA neurons. odr-10 mutants
fail to respond selectively to diacetyl and the odr-10
gene product is localized to the sensory cilia of the
AWA neurons. Expression of odr-10 under a heterologous
promoter restores responses to diacetyl, but not to other
odorants sensed by the AWA neurons. I plan to further
examine the regulation of odr-10 by odr-7, and
identify other genes that may also regulate odr-10
expression and function. Additionally, I am examining
how odr-7 specifies AWA function, by identifying
genes that act upstream and other genes downstream of
odr-7.
In addition
to odr-10, several large families of genes encoding
putative chemosensory receptors in the worm have been
identified (3). Analysis of the expression patterns of
some of these genes has shown that these genes are expressed
in small subsets of chemosensory neurons. I am using the
candidate chemosensory receptor genes as markers to determine
how the fates and functions of other chemosensory neurons
in the worm are determined. Using genetic screens and
behavioral assays, I will identify genes that are required
for the development and function of these neurons, as
defined by the expression of the appropriate receptor
genes.
I am also interested
in investiga-ting the roles of nuclear receptors in the
development of the worm sensory system. Although nuclear
receptors have been implicated in pattern formation and
tissue differentiation in many organisms, their roles
in the development of the worm are largely unknown. I
am exploring the possibility that odr-7-like genes
function to specify other sensory cell types in the worm.
We have identified several predicted genes that are homologous
to odr-7 in the worm genome sequence database (4).
One of these genes, nhr-22, is expressed in multiple
sensory neuron types. I am taking a reverse genetic approach
to understand the roles of nhr-22 and other odr-7-like
genes in the development and function of chemosensory
neurons in the worm.
