The olfactory bulb (OB) is the first relay station of olfactory information in the central nervous system (CNS).The general laminar organization and elaborate morphologies of OB projection neurons, mitral/tufted cells,have been well known for several decades, but we continue to lack insight into their developmentalmechanisms. Previous studies revealed the timeline of anatomical changes of developing mitral cells.The next step is to understand the molecular determinants and pathways regulating the specific anatomicalchanges occurring during mitral/tufted cell development, which is the long-term goal of this project. Toaccomplish this goal, I have established a novel method to manipulate molecular expression in subsets ofdeveloping mitral cells. Using this method, this proposal seeks to investigate the roles of several candidatemolecules in mitral cell development. The candidate molecules are three transcription factors (Tbr1, Tbr2,Tbx21), an extracellular matrix molecule (Reelin), a transmembrane protein (Protocadherin21), and asynaptic vesicle protein (vGluT1). All of these candidate molecules have been selected because they arespecifically expressed by mitral/tufted cells in developing OB.
In Aim 1, the temporal expression pattern ofcandidate molecules in developing mitral cells will be established.
In Aim 2, the fate of mitral cellprecursors in the absence of Tbr1 or Tbr2 will be determined.
In Aim 3, I will test hypotheses regarding theroles of Tbx21, Reelin, Protocadherin21, and vGluT1 in morphological development and/or synapseformation of mitral cells. These studies will provide us with new significant insights into moleculardeterminants and pathways working in developing mitral cells, which can then serve as a stepping stone tofurther research. I believe that this will become one of the leading works for neuronal circuitry formationduring development of both the OB and elsewhere in the CNS where these molecules are expressed.

Public Health Relevance

Olfactory information is transmitted to diverse brain regions through mitral/tufted cells in theolfactory bulb. Several developmental disorders also have olfactory dysfunctions: for example;many Asperger's syndrome children have hyperosima (increased ability to smell) or hyposmia(reduced ability to smell); and Kallmann syndrome patients have anosmia (inability to smell). Thegeneral goal of this project is to understand the developmental mechanisms of mitral/tufted cellswhich could help in finding a cure of these olfactory dysfunctions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
7R03DC011134-04
Application #
8793240
Study Section
Special Emphasis Panel (ZDC1-SRB-Q (69))
Program Officer
Sullivan, Susan L
Project Start
2010-06-01
Project End
2014-05-31
Budget Start
2014-01-18
Budget End
2014-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$84,145
Indirect Cost
$29,148
Name
Pennsylvania State University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
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