|
McClintock Lab: Neurogenomics of Olfaction and Neural Regeneration
Tim McClintock
Louis Boyarsky Professor of Physiology, University of Kentucky
Staff
- Neeraja Sammeta, Ph.D
- Soma C. Bose, M.S.
- Melissa Nickel
- Debra L. Hardin
- Jeremy C. McIntyre
Download Data Here
Olfactory physiology and neurogenesis
The olfactory system does two unique things: It detects odors and it continuously replaces injured neurons even in adults by
activating local progenitor basal cells. We investigate the molecular physiology of both of these processes. We use physiological
genomics techniques, such as microarrays, to observe system-wide effects and then use techniques focused on individual processes
or genes, such as targeted gene deletion, electrophysiology, biochemistry, and anatomy to plumb the depths of regulatory
networks of proteins controlling function.
Mouse olfactory sensory neurons: Gene expression and phenotype. Our studies of the membrane trafficking of odorant receptors
indicated the presence of olfactory-specific receptor trafficking proteins (Gimelbrant et al., 1999; 2001) that led to
investigation of gene expression in purified olfactory sensory neurons. A small-scale analysis yielded new cell-type
specific markers not only for mature olfactory sensory neurons, but also for sustentacular cells and respiratory epithelium
(Yu et al., 2005). A more comprehensive analysis coupled with extensive in situ hybridization data revealed that mature olfactory
sensory neurons express more than 10,000 genes (Sammeta et al., 2007). These data predict not only candidate genes for known
functions but also entire biological processes that are active in olfactory sensory neurons. An Excel file of these data is
available (click here to download the data).
Mouse olfactory cilia genes: Cilia are critical to the odor detection by olfactory sensory neurons, and to developmental and
signaling functions in other organ systems. Using bioinformatics methods based on tissue and cell expression patterns, we have
predicted new mouse cilia genes (McClintock et al., 2008). In general, these genes are highly expressed in olfactory sensory
neurons (click here to download the data).
Mouse olfactory neurogenesis: We have also investigated the molecular changes that underlie adult olfactory neurogenesis, finding
that the major molecular changes mirror the temporal changes in cell proliferation and phenotype that occur as the mature neurons
die and are subsequently replaced (Shetty et al., 2005; data available at GEO, accession # GSE2437). We also found that the molecular
changes that drive adult olfactory neurogenesis are highly similar to embryonic neurogenesis in the brain.
Lobster olfaction: Molecular physiology and neurogenesis. Lobsters provide several advantages for investigating the physiology and
biochemistry of olfactory transduction. We have cloned and characterized several components of the dual olfactory transduction
pathways used by lobsters (McClintock et al., 1997; Xu et al., 1997; 1998; 1999; Xu and McClintock, 1999). Our studies of gene
expression in the lobster olfactory organ have more recently expanded to include the identification of olfactory-specific mRNAs and of
genes responsive to stimuli that induce adult neurogenesis (Hollins et al., 2003; Stoss et al., 2004; Stepanyan et al., 2005). To futher
extend this avenue of investigation, we collaborated with the laboratories of Barry Ache (University of Florida) and Charles Derby
(Georgia State University) to clone and sequence more than 5,000 cDNAs from a subtracted EST library made from the mature zone of the
olfactory organ. These sequences and the BLAST searches used to identify them are available for downloading
(click here to download the data).
|
