Lingual deficits in neurotrophin double knockout mice
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Brain-derived neurotrophic factor (BDNF) and Neurotrophin 3 (NT-3) are members of the neurotrophin family and are expressed in the developing and adult tongue papillae. BDNF null-mutated mice exhibit specific impairments related to innervation and development of the gustatory system while NT-3 null mice have deficits in their lingual somatosensory innervation. To further evaluate the functional specificity of these neurotrophins in the peripheral gustatory system, we generated double BDNF/NT-3 knockout mice and compared the phenotype to BDNF−/− and wild-type mice. Taste papillae morphology was severely distorted in BDNF−/−xNT-3−/− mice compared to single BDNF−/− and wild-type mice. The deficits were found throughout the tongue and all gustatory papillae. There was a significant loss of fungiform papillae and the papillae were smaller in size compared to BDNF−/− and wild-type mice. Circumvallate papillae in the double knockouts were smaller and did not contain any intraepithelial nerve fibers. BDNF−/−xNT-3−/− mice exhibited additive losses in both somatosensory and gustatory innervation indicating that BDNF and NT-3 exert specific roles in the innervation of the tongue. However, the additional loss of fungiform papillae and taste buds in BDNF−/−xNT-3−/− mice compared to single BDNF knockout mice indicate a synergistic functional role for both BDNF-dependent gustatory and NT-3-dependent somatosensory innervations in taste bud and taste papillae innervation and development.
KeywordsKnockout Mouse Double Knockout Double Knockout Mouse Fungiform Papilla Gustatory System
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- AGERMAN, K., HJERLING-LEFFLER, J., BLANCHARD, M. P., SCARFONE, E., CANLON, B., NOSRAT, C. & ERNFORS, P. (2003) BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development. Development 130, 1479–1491.CrossRefPubMedGoogle Scholar
- CHOI, S., YATES, P. A. & O'LEARY, D. D. M. (1998) Localized BDNF application induces branch-like structures along retinal axons. Society of Neuroscience Abstract 24, 27.Google Scholar
- GANCHROW, D., GANCHROW, J. R., VERDIN-ALCAZAR, M. & WHITEHEAD, M. C. (2003a) Brain-derived neurotrophic factor-, neurotrophin-3-, and tyrosine kinase receptor-like immunoreactivity in lingual taste bud fields of mature hamster. Journal of Comparative Neurology 455, 11–24.Google Scholar
- GANCHROW, D., GANCHROW, J. R., VERDIN-ALCAZAR, M. & WHITEHEAD, M. C. (2003b) Brain-derived neurotrophic factor-, neurotrophin-3-, and tyrosine kinase receptor-like immunoreactivity in lingual taste bud fields of mature hamster after sensory denervation. Journal of Comparative Neurology 455, 25–39.Google Scholar
- HÖUKFELT, T., FUXE, K., GOLDSTEIN, M. & JOH, T. H. (1973) Immunohistochemical localization of three catecholamine synthesizing enzymes: aspects on methodology. Histochemie 33, 231–254.Google Scholar
- MISTRETTA, C. M., GOOSENS, K. A., FARINAS, I. & REICHARDT, L. F. (1999) Alterations in size, number, and morphology of gustatory papillae and taste buds in BDNF null mutant mice demonstrate neural dependence of developing taste organs. Journal of Comparative Neurology 409, 13–24.CrossRefPubMedGoogle Scholar
- MISTRETTA, C. M., LIU, H. X., GAFFIELD, W. & MACCALLUM, D. K. (2003) Cyclopamine and jervine in embryonic rat tongue cultures demonstrate a role for Shh signaling in taste papilla development and patterning: fungiform papillae double in number and form in novel locations in dorsal lingual epithelium. Developmental Biology 254, 1–18.CrossRefPubMedGoogle Scholar
- NOSRAT, C. A. (1998) Neurotrophic factors in the tongue; expression patterns, biological activity, relation to innervation and studies of neurotrophin knockout mice. Annals of the New York Academy of Science 855, 28– 50.Google Scholar
- NOSRAT, C. A., EBENDAL, T. & OLSON, L. (1996) Differential expression of brain-derived neurotrophic factor and neurotrophin 3 mRNA in lingual papillae and taste buds indicates roles in gustatory and somatosensory innervation. Journal of Comparative Neurology 376, 587– 602.CrossRefPubMedGoogle Scholar
- SEGAL, R. A. (2003) Selectivity in Neurotrophin Signaling: Theme and Variations. Annual Reviews in Neuroscience 18, 18.Google Scholar
- STONE, L. M., FINGER, T. E., TAM, P. & TAN, S. S. (1995) Taste receptor cells arise from local epithelium, not neurogenic ectoderm. Proceedings of the National Academy of Sciences USA 92, 1916–1920.Google Scholar