The morphogenesis of mouse vallate gustatory epithelium and taste buds requires BDNF-dependent taste neurons

Oakley, Bruce; Brandemihl, Adam; Cooper, Dylan; Lau, David H.; Lawton, Anne; Zhang, Chunxiao

doi:10.1016/s0165-3806(97)00178-8

Cited by 64 publications

(63 citation statements)

References 53 publications

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“…Unexpectedly, the lingual gustatory deficits seen in BDNFtransgenic mice have a remarkable resemblance to those previously described in BDN F knock-out mice (Nosrat et al, 1997a;Zhang et al, 1997;Oakley et al, 1998). Although mice overexpressing BDNF showed an increased number of neurons in cranial ganglia, BDNF knock-out mice display a distinct loss of neuronal cells, including a subpopulation of gustatory neurons (Ernfors et al, 1994a;Jones et al, 1994;Liu et al, 1995).…”

Section: Discussionsupporting

confidence: 65%

Role of Brain-Derived Neurotrophic Factor in Target Invasion in the Gustatory System

1999

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Brain-derived neurotrophic factor (BDNF) is a survival factor for different classes of neurons, including gustatory neurons. We have studied innervation and development of the gustatory system in transgenic mice overexpressing BDNF under the control of regulatory sequences from the nestin gene, an intermediate filament gene expressed in precursor cells of the developing nervous system and muscle. In transgenic mice, the number and size of gustatory papillae were decreased, circumvallate papillae had a deranged morphology, and there was also a severe loss of lingual taste buds. Paradoxically, similar deficits have been found in BDNF knock-out mice, which lack gustatory neurons. However, the number of neurons in gustatory ganglia was increased in BDNF-overproducing mice. Although gustatory fibers reached the tongue in normal numbers, the amount and density of nerve fibers in gustatory papillae were reduced in transgenic mice compared with wild-type littermates. Gustatory fibers appeared stalled at the base of the tongue, a site of ectopic BDNF expression, where they formed abnormal branches and sprouts. Interestingly, palatal taste buds, which are innervated by gustatory neurons whose afferents do not traverse sites of ectopic BDNF expression, appeared unaffected. We suggest that lingual gustatory deficits in BDNF overexpressing mice are a consequence of the failure of their BDNF-dependent afferents to reach their targets because of the effects of ectopically expressed BDNF on fiber growth. Our findings suggest that mammalian taste buds and gustatory papillae require proper BDNF-dependent gustatory innervation for development and that the correct spatial expression of BDNF in the tongue epithelium is crucial for appropriate target invasion and innervation. Key words: taste buds; gustatory; neurotrophins; gustation; transgenic; innervationThe peripheral gustatory system offers an interesting model for the study of target innervation and interaction between ingrowing nerves and neurotrophins. Developmental and experimental studies of gustatory papillae and taste buds have also offered information about the mechanisms underlying sensory organ development and maintenance in the tongue. Lingual papillae cover the dorsal surface of the tongue in mammals. Lingual gustatory papillae, namely f ungiform, circumvallate, and foliate papillae contain taste buds that are specialized peripheral sensory organs involved in perceiving chemical stimuli and in taste transduction. Fungiform papillae are located on the anterior dorsal surface of the tongue, and a single circumvallate papilla is located in the midline at the posterior part of the tongue in rodents. Lingual taste buds are innervated by nerve cells residing in the geniculate and petrosal ganglia. The somatosensory innervation of the posterior part of the tongue is derived from the petrosal ganglion, whereas trigeminal neurons provide somatosensory innervation to the anterior part of the tongue. Gustatory nerves innervate taste receptor cells in taste buds, whereas the sur...

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Section: Discussionsupporting

confidence: 65%

Role of Brain-Derived Neurotrophic Factor in Target Invasion in the Gustatory System

1999

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“…However, which factor or factors is key to promoting taste cell regeneration or taste cell differentiation in our cultured system merits further investigation. Prominent candidate growth factors may include brain-derived neurotrophic factor, nerve growth factor, neurotrophin-4, and R-spondins, among many others (30)(31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo

Ren

Lewandowski

Watson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

182

189

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Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues. Recently, we and others have shown that Lgr5 marks adult taste stem/progenitor cells in posterior tongue. However, the regenerative potential of Lgr5-expressing (Lgr5 + ) cells and the identity of adult taste stem/progenitor cells that regenerate taste tissue in anterior tongue remain elusive. In the present work, we describe a culture system in which single isolated Lgr5 + or Lgr6 + cells from taste tissue can generate continuously expanding 3D structures ("organoids"). Many cells within these taste organoids were cycling and positive for proliferative cell markers, cytokeratin K5 and Sox2, and incorporated 5-bromo-2'-deoxyuridine. Importantly, mature taste receptor cells that express gustducin, carbonic anhydrase 4, taste receptor type 1 member 3, nucleoside triphosphate diphosphohydrolase-2, or cytokeratin K8 were present in the taste organoids. Using calcium imaging assays, we found that cells grown out from taste organoids derived from isolated Lgr5 + cells were functional and responded to tastants in a dose-dependent manner. Genetic lineage tracing showed that Lgr6 + cells gave rise to taste bud cells in taste papillae in both anterior and posterior tongue. RT-PCR data demonstrated that Lgr5 and Lgr6 may mark the same subset of taste stem/progenitor cells both anteriorly and posteriorly. Together, our data demonstrate that functional taste cells can be generated ex vivo from single Lgr5 + or Lgr6 + cells, validating the use of this model for the study of taste cell generation. Lgr5 (leucine-rich repeat-containing G protein-coupled receptor 5), encoded by a Wnt (wingless-type MMTV integration site family) target gene, marks adult stem/progenitor cells in taste tissue in posterior tongue that in vivo give rise to all major types of taste bud cells, as well as perigemmal cells (6, 7). Lgr5 is also known to mark actively cycling stem cells in small intestine, colon, stomach, and hair follicle, as well as quiescent stem cells in liver, pancreas, and cochlea (8). Isolated Lgr5 + adult stem cells from multiple tissues are able to generate so-called organoid structures ex vivo (9-11). For instance, Sato and colleagues (10) developed a 3D culture system to grow crypt-villus organoids from single intestinal stem cells; all differentiated cell types were found in these structures, indicating the multipotent nature of these cells. We hypothesized that Lgr5 + taste stem/progenitor cells in a 3D culture system would be capable of expanding and giving rise to taste receptor cells ex vivo. In the present study, we isolated Lgr5 + stem/progenitor cells from taste tissue and cultured them in a 3D culture system. Single Lgr5 + cells grew into organoid structures ex vivo in defined culture conditions, with the presence of both proliferating cells and differentiated mature taste cells in which taste signaling components are functionally expressed. When organoids were replated onto a 2D sur...

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“…Moreover, BDNF is expressed in both emerging taste buds and in ganglion cells embryonically (Nosrat and Olson, 1995;Nosrat et al, 1996;Huang and Krimm, 2010) and at adulthood (Nosrat et al, 1997;Yee et al, 2003), indicating its potential life-long involvement in peripheral gustatory system organization. Genetically deleting BDNF or its receptor (TrkB) globally during early development dramatically decreases the normal numbers of taste buds and the number of neurons surviving to adulthood (Fritzsch et al, 1997;Nosrat et al, 1997;Oakley et al, 1998;Oakley, 1998;Patel and Krimm, 2010;Patel et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Expanded Terminal Fields of Gustatory Nerves Accompany Embryonic BDNF Overexpression in Mouse Oral Epithelia

2015

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Brain-derived neurotrophic factor (BDNF) is expressed in gustatory epithelia and is required for gustatory neurons to locate and innervate their correct target during development. When BDNF is overexpressed throughout the lingual epithelium, beginning embryonically, chorda tympani fibers are misdirected and innervate inappropriate targets, leading to a loss of taste buds. The remaining taste buds are hyperinnervated, demonstrating a disruption of nerve/target matching in the tongue. We tested the hypothesis here that overexpression of BDNF peripherally leads to a disrupted terminal field organization of nerves that carry taste information to the brainstem. The chorda tympani, greater superficial petrosal, and glossopharyngeal nerves were labeled in adult wild-type (WT) mice and in adult mice in which BDNF was overexpressed (OE) to examine the volume and density of their central projections in the nucleus of the solitary tract. We found that the terminal fields of the chorda tympani and greater superficial petrosal nerves and overlapping fields that included these nerves in OE mice were at least 80% greater than the respective field volumes in WT mice. The shapes of terminal fields were similar between the two groups; however, the density and spread of labels were greater in OE mice. Unexpectedly, there were also group-related differences in chorda tympani nerve function, with OE mice showing a greater relative taste response to a concentration series of sucrose. Overall, our results show that disruption in peripheral innervation patterns of sensory neurons have significant effects on peripheral nerve function and central organization of their terminal fields.

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The morphogenesis of mouse vallate gustatory epithelium and taste buds requires BDNF-dependent taste neurons

Cited by 64 publications

References 53 publications

Role of Brain-Derived Neurotrophic Factor in Target Invasion in the Gustatory System

Role of Brain-Derived Neurotrophic Factor in Target Invasion in the Gustatory System

Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo

Expanded Terminal Fields of Gustatory Nerves Accompany Embryonic BDNF Overexpression in Mouse Oral Epithelia

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