The neurotrophin (BDNF) is essential for the development and proper innervation of taste buds. Analysis of the taste system in wildtype and overexpresser transgenic mouse models has shown that BDNF acts, at least in part, as a target-derived factor that modulates axon targeting and innervation density. During early embryonic periods, BDNF is expressed in the epithelium of fungiform papillae. By later embryonic times BDNF expression in the tongue becomes focused and is only found in cells comprising developing taste buds. This refined expression pattern suggests that BDNF synthesis by taste bud cells is crucial for normal taste innervation. In support of this possibility, we found that transgenic mice that overexpress BDNF across the entire tongue epithelium had severely disrupted innervation to taste buds and fewer taste buds, even though these mice had more gustatory (geniculate) neurons. We now propose to advance this analysis and test how the level of BDNF in the taste bud itself affects neuron survival and innervation. This will be done using a new transgenic mouse model in which the keratin 19-gene promoter will be used to target BDNF gene expression to receptor cells of taste buds. Transgenic mice that overexpress K19 in taste cells (K19-BDNF mice) will be used to examine how target-derived BDNF modulates taste bud development and innervation. Specifically, we will use RT-PCR, in situ hybridization, retrograde labeling, and basic histological approaches to determine if enhanced expression of BDNF in taste cells, 1) increases innervation to fungiform papillae, 2) increases the size or number of taste buds in fungiform papillae, 3) disrupts the positive co-relation that exists between taste bud size and innervation, and 4) increases gelliculate ganglion cell survival. These mice will also provide a valuable model for studies on the receptor mechanisms and internal signaling pathways that underlie the action of BDNF in gustatory development. This approach provides a new and powerful means to manipulate gene expression in the taste end organs, allowing study of the intrinsic factors that regulate taste organ development and innervation.
| Lopez, Grace F; Krimm, Robin F (2006) Epithelial overexpression of BDNF and NT4 produces distinct gustatory axon morphologies that disrupt initial targeting. Dev Biol 292:457-68 |
