Taste buds are multicellular receptor organs of the gustatory system, and are innervated by a discrete set of cranial nerves. For nearly a century, taste buds were believed to form late in embryonic development following induction by nerves. However, recent findings have shifted this view dramatically. Early taste bud development is not dependent upon nerves. Further, taste buds arise via processes intrinsic to the tongue, _rocesses that occur long before taste buds differentiate. Most recently, we have demonstrated that .=pithelium destined to give to taste buds, the pharyngeal endoderm, receives signals very early, during gastrulation, that initially specify, or direct the fate of, this embryonic tissue. Further, cell-cell interactions within this specified endoderm regulate the subsequent patterning of this epithelium so that it gives rise to a distributed array of taste buds. We are now poised to expand substantially on our earlier model, and test detailed hypotheses concerning these key early events in taste bud development. In this proposal, molecular and cellular mechanisms which first specify (fate is directed but still reversible) and then determine (fate is irreversibly selected) the ability of pharyngeal endoderm to generate taste buds will be assessed. An additional question addressed in this aim is whether the same signals are responsible for both processes (Aim 1). Studies of taste bud patterning will be expanded to the molecular realm, to determine if, based upon suggestive gene expression patterns, the Notch signaling pathway is involved in patterning taste buds (Aim 2). Finally, to meld data from mammalian taste bud development with our own, genes known to be present in developing taste organs of mice will be cloned from axolotls and expression of these gene products will be explored in the developing taste epithelium of axolotls. By comparing gene expression patterns across species, we will identify genes associated in general with taste bud development (Aim 3).

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Somatosensory and Chemosensory Systems Study Section (SCS)
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Davis, Barry
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University of Colorado Denver
Schools of Medicine
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Miura, Hirohito; Scott, Jennifer K; Harada, Shuitsu et al. (2014) Sonic hedgehog-expressing basal cells are general post-mitotic precursors of functional taste receptor cells. Dev Dyn 243:1286-97
Kapsimali, Marika; Barlow, Linda A (2013) Developing a sense of taste. Semin Cell Dev Biol 24:200-9
Nguyen, Ha M; Reyland, Mary E; Barlow, Linda A (2012) Mechanisms of taste bud cell loss after head and neck irradiation. J Neurosci 32:3474-84
Harlow, Danielle E; Yang, Hui; Williams, Trevor et al. (2011) Epibranchial placode-derived neurons produce BDNF required for early sensory neuron development. Dev Dyn 240:309-23
Miura, H; Barlow, L A (2010) Taste bud regeneration and the search for taste progenitor cells. Arch Ital Biol 148:107-18
Nguyen, Ha M; Barlow, Linda A (2010) Differential expression of a BMP4 reporter allele in anterior fungiform versus posterior circumvallate taste buds of mice. BMC Neurosci 11:129
Liu, Fei; Thirumangalathu, Shoba; Gallant, Natalie M et al. (2007) Wnt-beta-catenin signaling initiates taste papilla development. Nat Genet 39:106-12
Harlow, Danielle E; Barlow, Linda A (2007) Embryonic origin of gustatory cranial sensory neurons. Dev Biol 310:317-28
Seta, Yuji; Stoick-Cooper, Cristi L; Toyono, Takashi et al. (2006) The bHLH transcription factors, Hes6 and Mash1, are expressed in distinct subsets of cells within adult mouse taste buds. Arch Histol Cytol 69:189-98
Parker, Mark A; Bell, Melanie L; Barlow, Linda A (2004) Cell contact-dependent mechanisms specify taste bud pattern during a critical period early in embryonic development. Dev Dyn 230:630-42

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