During development, gustatory innervation is a tightly regulated process in which specific numbers of primary taste afferents project to discrete regions of the oral cavity. The present research is designed to investigate gustatory innervation in support of two long terms goals: 1) to determine the cellular and molecular mechanisms that allow gustatory neurons to innervate the correct target (taste buds) with a specific mount of innervation, and 2) to determine if and/or how these connections are important for central gustatory development or taste function. The proposed project focuses on the role of neurotrophins in regulating gustatory neuron number and peripheral and central targeting during embryonic development. It is known that the number of gustatory ganglion neurons that will exist at birth to innervate taste buds on the tongue and palate is somehow determined by brain-derived neurotrophic factor (BDNI0 and neurotrophin-4 (NT4). However, the mechanism(s) by which BDNF and NT4 regulate innervation are unknown, and could involve any number of different developmental processes during numerous different embryonic stages. The proposed studies combine in situ hybridization, cell counting, tract tracing, immunohistochemistry, and SEM in gene knockout mice to: 1) determine when and where the embryonic taste system is exposed to BDNF and NT4, 2) determine when BDNF and NT4 regulate gustatory neuron number and whether this regulation is accomplished by reducing proliferation or by increasing cell death, 3) determine whether BDNF and/or NT4 is required for initial target invasion, and 4) determine if BDNF and/or NT4 regulate the central distribution of tongue and palatal sensory afferents. Together, these studies test the hypotheses that: 1) NT4 is expressed along gustatory fiber projection pathways and regulates gustatory neuron survival before initial innervation of peripheral and central targets, and 2) BDNF is expressed in gustatory epithelia and regulates neuron survival after initial peripheral and central target innervation. Because these experiments examine how neurotrophins regulate the amount and location of sensory innervation, this project has important implications for the potential therapeutic use of these powerful signaling molecules in controlling neural regeneration following injury.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC007176-04
Application #
7365189
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Davis, Barry
Project Start
2005-03-01
Project End
2010-06-30
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
4
Fiscal Year
2008
Total Cost
$309,180
Indirect Cost
Name
University of Louisville
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Sun, Chengsan; Krimm, Robin; Hill, David L (2018) Maintenance of Mouse Gustatory Terminal Field Organization is Dependent on BDNF at Adulthood. J Neurosci :
Tang, Tao; Rios-Pilier, Jennifer; Krimm, Robin (2017) Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers. Mol Cell Neurosci 82:195-203
Ohman-Gault, Lisa; Huang, Tao; Krimm, Robin (2017) The transcription factor Phox2b distinguishes between oral and non-oral sensory neurons in the geniculate ganglion. J Comp Neurol 525:3935-3950
Meng, Lingbin; Huang, Tao; Sun, Chengsan et al. (2017) BDNF is required for taste axon regeneration following unilateral chorda tympani nerve section. Exp Neurol 293:27-42
Biggs, Bradley T; Tang, Tao; Krimm, Robin F (2016) Insulin-Like Growth Factors Are Expressed in the Taste System, but Do Not Maintain Adult Taste Buds. PLoS One 11:e0148315
Meng, Lingbin; Ohman-Gault, Lisa; Ma, Liqun et al. (2015) Taste Bud-Derived BDNF Is Required to Maintain Normal Amounts of Innervation to Adult Taste Buds. eNeuro 2:
Sun, Chengsan; Dayal, Arjun; Hill, David L (2015) Expanded terminal fields of gustatory nerves accompany embryonic BDNF overexpression in mouse oral epithelia. J Neurosci 35:409-21
Huang, Tao; Ma, Liqun; Krimm, Robin F (2015) Postnatal reduction of BDNF regulates the developmental remodeling of taste bud innervation. Dev Biol 405:225-36
Huang, Tao; Krimm, Robin F (2014) BDNF and NT4 play interchangeable roles in gustatory development. Dev Biol 386:308-20
Patel, Ami V; Krimm, Robin F (2012) Neurotrophin-4 regulates the survival of gustatory neurons earlier in development using a different mechanism than brain-derived neurotrophic factor. Dev Biol 365:50-60

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