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. Brain-derived neurotrophic factor (BDNF) regulates both the number and location of gustatory innervation during embryonic development. Our current research is designed to determine if and/or how these connections are important for central gustatory development or taste function and whether BDNF regulates development of the postnatal taste system. The proposed studies combine cell counting, tract tracing, immunohistochemistry, electrophysiology, and behavioral testing in conditional and inducible transgenic mice to: 1) determine if BDNF influences postnatal changes in geniculate ganglion and taste bud development, 2) determine if embryonic or postnatal BDNF is important for central terminal field organization, and 3) determine if embryonic or postnatal BDNF is important for adult gustatory function. Together, these studies test the hypotheses that: 1) embryonic BDNF determines the number of neurons innervating a taste bud, and taste buds increase in size to meet that number postnatally. 2) CNS terminal field formation is regulated by BDNF and the specificity of peripheral connections. 3) Gustatory sensitivity is reduced but that the taste system still functions despite wide-scale reorganization. These studies will determine how early peripheral innervation patterns influence continued development and function of the taste system. In addition, we will determine whether BDNF is required for postnatal gustatory development. Because these experiments examine how neurotrophin regulation of sensory innervation influences continued development and adult function, this project has important implications for the potential therapeutic use of these powerful signaling molecules in re-establishing gustatory function following neuronal impairment.
Taste disorders can have detrimental effects on a person's health and quality of life. According to NIDCD, more than 200,000 people visit a doctor each year for problems with their chemical senses, including taste. The underlying mechanism of many gustatory disruptions is not well understood. As a result, much emphasis has been placed on a basic understanding of the taste bud. However, the neurons innervating taste buds receive little attention and are also required for normal gustatory function. Some adult gustatory disruptions may result from an alteration in factor(s) regulating gustatory system innervation both during development and as a part of normal adult homeostasis. Peripheral neuropathies are relatively common and frequently accompany other illnesses. A basic understanding of the factors that are required to promote innervation during development and possibly maintain it in adulthood may lead to therapeutic approaches that allow taste recovery following its loss.
|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|
|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|
|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; 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|
|Jia, Haiqun; Pallos, Judit; Jacques, Vincent et al. (2012) Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate polyglutamine-elicited phenotypes in model systems of Huntington's disease. Neurobiol Dis 46:351-61|
|Patel, Ami V; Krimm, Robin F (2010) BDNF is required for the survival of differentiated geniculate ganglion neurons. Dev Biol 340:419-29|
|Huang, Tao; Krimm, Robin F (2010) Developmental expression of Bdnf, Ntf4/5, and TrkB in the mouse peripheral taste system. Dev Dyn 239:2637-46|
|Patel, Ami V; Huang, Tao; Krimm, Robin F (2010) Lingual and palatal gustatory afferents each depend on both BDNF and NT-4, but the dependence is greater for lingual than palatal afferents. J Comp Neurol 518:3290-301|
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