In the vertebrate olfactory system production of new sensory neurons continues throughout adult life. In any continuously renewing tissue a """"""""steady state"""""""" in total cell number is achieved by a balance between cell proliferation and cell death. This implies that: 1) the rate of cell proliferation is regulated, 2) the rate of cell death is regulated, and 3) the regulating factors for cell proliferation and cell death are linked. The overall aim of this proposal is to examine several aspects of cell proliferation and cell death in olfactory epithelium. Earlier experiments had shown that olfactory cell proliferation can be up-and down-regulated by experimental manipulations. Preliminary data implicate two growth factors, Epidermal Growth Factor (EGF) and Transforming Growth Factor-a (TGF-a), in up-regulation of cell proliferation in an in vitro assay. These are both members of what is called the EGF family of growth factors. The working hypothesis is that members of the EGF family of growth factors participate in the regulation of mitotic rate in olfactory epithelium. This proposal represents a multidisciplinary approach to the study of cellular dynamics in the olfactory sensory epithelium.
One aim i s to determine whether the EGF family of growth factors and their cognate receptors are functional participants in the regulation of olfactory (or supporting) cell proliferation both in vitro and in vivo. Another aim is to test other growth factors for their efficacy in enhancing proliferation in olfactory epithelium. Several techniques, including organ culture, immunohistochemistry, electron microscopy, in situ hybridization and biochemistry will be used in these experiments. The other aspect of how the olfactory cell population numbers are maintained is the regulation of cell death. Very little detailed information is available about the mechanism of cell death in the olfactory system. Part of this proposal is designed to obtain some baseline information; for example, electron microscope studies on cell death following ablation of the olfactory bulb will be done to acquire detailed information about the specific morphological changes that occur in dying cells and to determine the means for their disposal. The literature on cell death in other systems suggests that certain biochemical events are observable most of the time in cells that are programmed to die. Probes for the identification of cell death markers in other tissues will be used to specify the biochemical and histochemical markers for olfactory cell death. Finally growth factors will be infused into unilaterally bulbectomized rats by a micropumping apparatus to try to rescue olfactory cells that are destined to die.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002126-02
Application #
2127265
Study Section
Sensory Disorders and Language Study Section (CMS)
Project Start
1994-06-01
Project End
1997-05-31
Budget Start
1995-06-01
Budget End
1996-05-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201
Weiler, Elke (2005) Postnatal development of the rat vomeronasal organ. Chem Senses 30 Suppl 1:i127-8
Weiler, Elke; Farbman, Albert I (2003) The septal organ of the rat during postnatal development. Chem Senses 28:581-93
Carr, V M; Menco, B P; Yankova, M P et al. (2001) Odorants as cell-type specific activators of a heat shock response in the rat olfactory mucosa. J Comp Neurol 432:425-39
Farbman, A I; Buchholz, J A; Suzuki, Y et al. (1999) A molecular basis of cell death in olfactory epithelium. J Comp Neurol 414:306-14
Carr, V M; Morimoto, R I; Farbman, A I (1999) Development and further characterization of a small subclass of rat olfactory receptor neurons that shows immunoreactivity for the HSP70 heat shock protein. J Comp Neurol 404:375-86
Weiler, E; Apfelbach, R; Farbman, A I (1999) The vomeronasal organ of the male ferret. Chem Senses 24:127-36
Weiler, E; Farbman, A I (1999) Mitral cell loss following lateral olfactory tract transection increases proliferation density in rat olfactory epithelium. Eur J Neurosci 11:3265-75
Weiler, E; McCulloch, M A; Farbman, A I (1999) Proliferation in the vomeronasal organ of the rat during postnatal development. Eur J Neurosci 11:700-11
Carr, V M; Walters, E; Margolis, F L et al. (1998) An enhanced olfactory marker protein immunoreactivity in individual olfactory receptor neurons following olfactory bulbectomy may be related to increased neurogenesis. J Neurobiol 34:377-90
Weiler, E; Farbman, A I (1998) Proliferation decrease in the olfactory epithelium during postnatal development. Ann N Y Acad Sci 855:230-4

Showing the most recent 10 out of 14 publications