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Charlotte M Mistretta - One of the best experts on this subject based on the ideXlab platform.
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Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling.
Public Library of Science (PLoS), 2016Co-Authors: Alexandre N Ermilov, Archana Kumari, Ariell M Joiner, Marina A Grachtchouk, Benjamin L Allen, Andrzej A Dlugosz, Charlotte M MistrettaAbstract:For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate Papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste Papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in Papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings suggest that taste alterations in cancer patients using systemic Hedgehog pathway inhibitors result principally from interruption of signaling activity in taste Papillae
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fungiform papilla pattern egf regulates inter papilla lingual epithelium and decreases papilla number by means of pi3k akt mek erk and p38 mapk signaling
Developmental Dynamics, 2008Co-Authors: Hong Xiang Liu, Bradley S Henson, Yanqiu Zhou, Nisha J Dsilva, Charlotte M MistrettaAbstract:Fungiform Papillae are epithelial taste organs that form on the tongue, requiring differentiation of Papillae and inter-papilla epithelium. We tested roles of epidermal growth factor (EGF) and the receptor EGFR in papilla development. Developmentally, EGF was localized within and between Papillae whereas EGFR was progressively restricted to inter-papilla epithelium. In tongue cultures, EGF decreased Papillae and increased cell proliferation in inter-papilla epithelium in a concentration-dependent manner, whereas EGFR inhibitor increased and fused Papillae. EGF preincubation could over-ride disruption of Shh signaling that ordinarily would effect a doubling of fungiform Papillae. With EGF-induced activation of EGFR, we demonstrated phosphorylation in PI3K/Akt, MEK/ERK, and p38 MAPK pathways; with pathway inhibitors (LY294002, U0126, SB203580) the EGF-mediated decrease in Papillae was reversed, and synergistic actions were shown. Thus, EGF/EGFR signaling by means of PI3K/Akt, MEK/ERK, and p38 MAPK contributes to epithelial cell proliferation between Papillae; this biases against papilla differentiation and reduces numbers of Papillae. Developmental Dynamics 237:2378–2393, 2008. © 2008 Wiley-Liss, Inc.
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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, 2003Co-Authors: Charlotte M Mistretta, William Gaffield, Hong Xiang Liu, Donald K MaccallumAbstract:From time of embryonic emergence, the gustatory papilla types on the mammalian tongue have stereotypic anterior and posterior tongue locations. Furthermore, on anterior tongue, the fungiform Papillae are patterned in rows. Among the many molecules that have potential roles in regulating papilla location and pattern, Sonic hedgehog (Shh) has been localized within early tongue and developing Papillae. We used an embryonic, tongue organ culture system that retains temporal, spatial, and molecular characteristics of in vivo taste papilla morphogenesis and patterning to study the role of Shh in taste papilla development. Tongues from gestational day 14 rat embryos, when Papillae are just beginning to emerge on dorsal tongue, were maintained in organ culture for 2 days. The steroidal alkaloids, cyclopamine and jervine, that specifically disrupt the Shh signaling pathway, or a Shh-blocking antibody were added to the standard culture medium. Controls included tongues cultured in the standard medium alone, and with addition of solanidine, an alkaloid that resembles cyclopamine structurally but that does not disrupt Shh signaling. In cultures with cyclopamine, jervine, or blocking antibody, fungiform papilla numbers doubled on the dorsal tongue with a distribution that essentially eliminated inter-papilla regions, compared with tongues in standard medium or solanidine. In addition, fungiform Papillae developed on posterior oral tongue, just in front of and beside the single circumvallate papilla, regions where fungiform Papillae do not typically develop. The Shh protein was in all fungiform Papillae in embryonic tongues, and tongue cultures with standard medium or cyclopamine, and was conspicuously localized in the basement membrane region of the Papillae. Ptc protein had a similar distribution to Shh, although the immunoproduct was more diffuse. Fungiform Papillae did not develop on pharyngeal or ventral tongue in cyclopamine and jervine cultures, or in the tongue midline furrow, nor was development of the single circumvallate papilla altered. The results demonstrate a prominent role for Shh in fungiform papilla induction and patterning and indicate differences in morphogenetic control of fungiform and circumvallate papilla development and numbers. Furthermore, a previously unknown, broad competence of dorsal lingual epithelium to form fungiform Papillae on both anterior and posterior oral tongue is revealed.
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organ cultures of embryonic rat tongue support tongue and gustatory papilla morphogenesis in vitro without intact sensory ganglia
The Journal of Comparative Neurology, 1997Co-Authors: Josephpascal Mbiene, Donald K Maccallum, Charlotte M MistrettaAbstract:Taste buds on the mammalian tongue are confined to the epithelium of three types of gustatory Papillae: the fungiform, circumvallate, and foliate. The gustatory Papillae are composed of an epithelium that covers a broad connective tissue core, with extensive innervation to taste bud and nongustatory epithelial locations. Although the temporal sequence of gustatory papilla development is known for several species, factors that regulate initiation, growth, and maintenance of the Papillae are not understood. We tested the hypothesis that sensory innervation is required for the initial formation and early morphogenesis of fungiform Papillae in a patterned array. An organ culture of the embryonic rat tongue was developed to provide an in vitro system for studying mechanisms involved in fungiform papilla morphogenesis in patterns on the anterior tongue. Tongues were dissected from embryos at 13 days of gestation (E13), a time when the tongue has not yet fully formed and gustatory Papillae have not yet appeared, and at 14 days of gestation (E14), when the tongue is well formed and Papillae make their initial morphological appearance. Dissected tongues were maintained at the gas/liquid interface in standard organ culture dishes, fed with DMEM/F12 plus 2% B-27 supplement and 1% fetal bovine serum. After 1, 2, 3, or 6 days in culture, tongues were processed for scanning electron or light microscopy, or immunocytochemistry. Tongues cultured from E13 or E14 underwent extensive morphogenesis and growth in vitro. Furthermore, fungiform Papillae developed on these tongues on a culture day equivalent to E15 in vivo; that is, after 2 days for cultures begun at E13 and 1 day for those begun at E14. Because E15 is the characteristic time for gustatory papilla formation in the intact embryo, results demonstrate that the cultured tongues retain important temporal information related to papilla development. In addition, fungiform Papillae formed in the tongue cultures in the stereotypic pattern of rows. The Papillae were large structures with epithelial and mesenchymal cell integrity, and an intact epithelial basement membrane was indicated with laminin immunoreactivity. The cultures demonstrate that gustatory papilla morphogenesis can progress in the absence of an intact sensory innervation. To exclude a potential developmental role for autonomic ganglion cells that are located in the posterior rat tongue, cultures consisting of only the anterior half of E14 tongues were established. Fungiform papilla development progressed in half tongues in a manner directly comparable to whole tongue cultures. Therefore, robust, reproducible development of fungiform Papillae in patterns is supported in rat tongue cultures from E13 or E14, without inclusion of intact sensory or major, posterior tongue autonomic ganglia. This is direct evidence that Papillae will form and develop further in vitro without sensory ganglion support. The data also provide the first detailed account of in vitro development of the entire embryonic tongue.
Josephpascal Mbiene - One of the best experts on this subject based on the ideXlab platform.
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organ cultures of embryonic rat tongue support tongue and gustatory papilla morphogenesis in vitro without intact sensory ganglia
The Journal of Comparative Neurology, 1997Co-Authors: Josephpascal Mbiene, Donald K Maccallum, Charlotte M MistrettaAbstract:Taste buds on the mammalian tongue are confined to the epithelium of three types of gustatory Papillae: the fungiform, circumvallate, and foliate. The gustatory Papillae are composed of an epithelium that covers a broad connective tissue core, with extensive innervation to taste bud and nongustatory epithelial locations. Although the temporal sequence of gustatory papilla development is known for several species, factors that regulate initiation, growth, and maintenance of the Papillae are not understood. We tested the hypothesis that sensory innervation is required for the initial formation and early morphogenesis of fungiform Papillae in a patterned array. An organ culture of the embryonic rat tongue was developed to provide an in vitro system for studying mechanisms involved in fungiform papilla morphogenesis in patterns on the anterior tongue. Tongues were dissected from embryos at 13 days of gestation (E13), a time when the tongue has not yet fully formed and gustatory Papillae have not yet appeared, and at 14 days of gestation (E14), when the tongue is well formed and Papillae make their initial morphological appearance. Dissected tongues were maintained at the gas/liquid interface in standard organ culture dishes, fed with DMEM/F12 plus 2% B-27 supplement and 1% fetal bovine serum. After 1, 2, 3, or 6 days in culture, tongues were processed for scanning electron or light microscopy, or immunocytochemistry. Tongues cultured from E13 or E14 underwent extensive morphogenesis and growth in vitro. Furthermore, fungiform Papillae developed on these tongues on a culture day equivalent to E15 in vivo; that is, after 2 days for cultures begun at E13 and 1 day for those begun at E14. Because E15 is the characteristic time for gustatory papilla formation in the intact embryo, results demonstrate that the cultured tongues retain important temporal information related to papilla development. In addition, fungiform Papillae formed in the tongue cultures in the stereotypic pattern of rows. The Papillae were large structures with epithelial and mesenchymal cell integrity, and an intact epithelial basement membrane was indicated with laminin immunoreactivity. The cultures demonstrate that gustatory papilla morphogenesis can progress in the absence of an intact sensory innervation. To exclude a potential developmental role for autonomic ganglion cells that are located in the posterior rat tongue, cultures consisting of only the anterior half of E14 tongues were established. Fungiform papilla development progressed in half tongues in a manner directly comparable to whole tongue cultures. Therefore, robust, reproducible development of fungiform Papillae in patterns is supported in rat tongue cultures from E13 or E14, without inclusion of intact sensory or major, posterior tongue autonomic ganglia. This is direct evidence that Papillae will form and develop further in vitro without sensory ganglion support. The data also provide the first detailed account of in vitro development of the entire embryonic tongue.
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early development and innervation of taste bud bearing Papillae on the rat tongue
The Journal of Comparative Neurology, 1991Co-Authors: Albert I Farbman, Josephpascal MbieneAbstract:Early development of fungiform Papillae on the fetal rat tongue was examined: (1) to determine whether morphogenesis of the taste bud-bearing fungiform Papillae is induced by nerve and (2) to study the growth pattern of the two sensory nerves that innervate the papilla. The Papillae first appear on the 15th day of gestation (E15; E1 is the day when the dam is sperm positive) in rows parallel to the midline sulcus. There appears to be a medial-lateral and an anterior-posterior gradient in the sequence of papilla differentiation. The epithelium of the early papilla resembles a multilayered placode topped by a flattened surface periderm. Close examination of the peridermal cells at the apex of the Papillae reveals that the cells have fewer surface microvilli and their cytoplasm is more electron opaque than that of similar cells in interpapillary regions. The basal cells in the placode-like epithelium differ from those in interpapillary regions in that they are postmitotic and have more mitochondria. At later stages, the papilla acquires a mesenchymal core and nerves grow into the core. Results from organ culture experiments of tongue fragments taken from E14 fetuses indicate that morphogenesis of fungiform Papillae is initiated in the absence of sensory nerve influence, but the nerve exerts a trophic effect on their maintenance. The two sensory nerves of the tongue, the chorda tympani and the lingual branch of the trigeminal nerve, enter the tongue mesenchyme at E14 and grow toward the epithelium. By E15 the chorda tympani branches have reached the developing fungiform Papillae, by E16 many have entered the papilla, and by E17 they have penetrated the epithelium at the papilla apex. Their fibers are associated exclusively with the cells at the papilla apex, where the taste bud will develop. The trigeminal nerve ramifies beneath the surface of the entire epithelium by E15. Later, it, too, sends branches into fungiform Papillae; these ascend along the trunk of the chorda tympani and at E17 terminate in the connective tissue core around the chorda tympani field. The results are compatible with the notion that the tongue epithelium exerts a general tropic effect on growing axons of both sensory nerves, and the epithelial cells of the fungiform papilla apex exert a similar effect to which only the chorda tympani axons are responsive.
Donald K Maccallum - One of the best experts on this subject based on the ideXlab platform.
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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, 2003Co-Authors: Charlotte M Mistretta, William Gaffield, Hong Xiang Liu, Donald K MaccallumAbstract:From time of embryonic emergence, the gustatory papilla types on the mammalian tongue have stereotypic anterior and posterior tongue locations. Furthermore, on anterior tongue, the fungiform Papillae are patterned in rows. Among the many molecules that have potential roles in regulating papilla location and pattern, Sonic hedgehog (Shh) has been localized within early tongue and developing Papillae. We used an embryonic, tongue organ culture system that retains temporal, spatial, and molecular characteristics of in vivo taste papilla morphogenesis and patterning to study the role of Shh in taste papilla development. Tongues from gestational day 14 rat embryos, when Papillae are just beginning to emerge on dorsal tongue, were maintained in organ culture for 2 days. The steroidal alkaloids, cyclopamine and jervine, that specifically disrupt the Shh signaling pathway, or a Shh-blocking antibody were added to the standard culture medium. Controls included tongues cultured in the standard medium alone, and with addition of solanidine, an alkaloid that resembles cyclopamine structurally but that does not disrupt Shh signaling. In cultures with cyclopamine, jervine, or blocking antibody, fungiform papilla numbers doubled on the dorsal tongue with a distribution that essentially eliminated inter-papilla regions, compared with tongues in standard medium or solanidine. In addition, fungiform Papillae developed on posterior oral tongue, just in front of and beside the single circumvallate papilla, regions where fungiform Papillae do not typically develop. The Shh protein was in all fungiform Papillae in embryonic tongues, and tongue cultures with standard medium or cyclopamine, and was conspicuously localized in the basement membrane region of the Papillae. Ptc protein had a similar distribution to Shh, although the immunoproduct was more diffuse. Fungiform Papillae did not develop on pharyngeal or ventral tongue in cyclopamine and jervine cultures, or in the tongue midline furrow, nor was development of the single circumvallate papilla altered. The results demonstrate a prominent role for Shh in fungiform papilla induction and patterning and indicate differences in morphogenetic control of fungiform and circumvallate papilla development and numbers. Furthermore, a previously unknown, broad competence of dorsal lingual epithelium to form fungiform Papillae on both anterior and posterior oral tongue is revealed.
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organ cultures of embryonic rat tongue support tongue and gustatory papilla morphogenesis in vitro without intact sensory ganglia
The Journal of Comparative Neurology, 1997Co-Authors: Josephpascal Mbiene, Donald K Maccallum, Charlotte M MistrettaAbstract:Taste buds on the mammalian tongue are confined to the epithelium of three types of gustatory Papillae: the fungiform, circumvallate, and foliate. The gustatory Papillae are composed of an epithelium that covers a broad connective tissue core, with extensive innervation to taste bud and nongustatory epithelial locations. Although the temporal sequence of gustatory papilla development is known for several species, factors that regulate initiation, growth, and maintenance of the Papillae are not understood. We tested the hypothesis that sensory innervation is required for the initial formation and early morphogenesis of fungiform Papillae in a patterned array. An organ culture of the embryonic rat tongue was developed to provide an in vitro system for studying mechanisms involved in fungiform papilla morphogenesis in patterns on the anterior tongue. Tongues were dissected from embryos at 13 days of gestation (E13), a time when the tongue has not yet fully formed and gustatory Papillae have not yet appeared, and at 14 days of gestation (E14), when the tongue is well formed and Papillae make their initial morphological appearance. Dissected tongues were maintained at the gas/liquid interface in standard organ culture dishes, fed with DMEM/F12 plus 2% B-27 supplement and 1% fetal bovine serum. After 1, 2, 3, or 6 days in culture, tongues were processed for scanning electron or light microscopy, or immunocytochemistry. Tongues cultured from E13 or E14 underwent extensive morphogenesis and growth in vitro. Furthermore, fungiform Papillae developed on these tongues on a culture day equivalent to E15 in vivo; that is, after 2 days for cultures begun at E13 and 1 day for those begun at E14. Because E15 is the characteristic time for gustatory papilla formation in the intact embryo, results demonstrate that the cultured tongues retain important temporal information related to papilla development. In addition, fungiform Papillae formed in the tongue cultures in the stereotypic pattern of rows. The Papillae were large structures with epithelial and mesenchymal cell integrity, and an intact epithelial basement membrane was indicated with laminin immunoreactivity. The cultures demonstrate that gustatory papilla morphogenesis can progress in the absence of an intact sensory innervation. To exclude a potential developmental role for autonomic ganglion cells that are located in the posterior rat tongue, cultures consisting of only the anterior half of E14 tongues were established. Fungiform papilla development progressed in half tongues in a manner directly comparable to whole tongue cultures. Therefore, robust, reproducible development of fungiform Papillae in patterns is supported in rat tongue cultures from E13 or E14, without inclusion of intact sensory or major, posterior tongue autonomic ganglia. This is direct evidence that Papillae will form and develop further in vitro without sensory ganglion support. The data also provide the first detailed account of in vitro development of the entire embryonic tongue.
Wheilin Pan - One of the best experts on this subject based on the ideXlab platform.
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factors influencing the presence of interproximal dental Papillae between maxillary anterior teeth
Journal of Periodontology, 2010Co-Authors: Minchieh Chen, Yufang Liao, Chiupo Chan, Wheilin PanAbstract:Background: The presence of interdental Papillae in the maxillary anterior region plays a key esthetic role. The aim of this study is to investigate the impact of demographic variables, such as gender and ages, and radiographic measurements of interdental area anatomy on the presence of interdental Papillae.Methods: Periapical radiographs of 102 interdental Papillae between maxillary anterior teeth were obtained in 30 adults who had fully erupted permanent dentition, healthy gingiva, and well-aligned maxillary anterior teeth. A radiopaque material was placed on the tip of the interdental papilla and the mucogingival junction. Radiographic measurements of tooth shape, alveolar bone level, and interdental space anatomy were undertaken using computer software.Results: When each factor was evaluated individually, the shorter the distance between the contact bone and alveolar bone crest, the shorter the distance between two adjacent teeth, and the smaller the embrasure area, the more likely interdental papilla...
Heiko Peters - One of the best experts on this subject based on the ideXlab platform.
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The Formation of Endoderm-Derived Taste Sensory Organs Requires a Pax9-Dependent Expansion of Embryonic Taste Bud Progenitor Cells
2016Co-Authors: Ralf Kist, Michelle Watson, Moira Crosier, Max Robinson, Jennifer Fuchs, Julia Reichelt, Heiko PetersAbstract:In mammals, taste buds develop in different regions of the oral cavity. Small epithelial protrusions form fungiform Papillae on the ectoderm-derived dorsum of the tongue and contain one or few taste buds, while taste buds in the soft palate develop without distinct papilla structures. In contrast, the endoderm-derived circumvallate and foliate Papillae located at the back of the tongue contain a large number of taste buds. These taste buds cluster in deep epithelial trenches, which are generated by intercalating a period of epithelial growth between initial placode formation and conversion of epithelial cells into sensory cells. How epithelial trench formation is genetically regulated during development is largely unknown. Here we show that Pax9 acts upstream of Pax1 and Sox9 in the expanding taste progenitor field of the mouse circumvallate papilla. While a reduced number of taste buds develop in a growth-retarded circumvallate papilla of Pax1 mutant mice, its development arrests completely in Pax9-deficient mice. In addition, the Pax9 mutant circumvallate papilla trenches lack expression of K8 and Prox1 in the taste bud progenitor cells, and gradually differentiate into an epidermal-like epithelium. We also demonstrate that taste placodes of the soft palate develop through a Pax9-dependent induction. Unexpectedly, Pax9 is dispensable for patterning, morphogenesis and maintenance of taste buds that develop in ectoderm-derived fungiform Papillae. Collectively, our data reveal an endoderm-specific developmental program for the formation of taste buds and their associated papilla structures. In this pathway, Pax9 is essential to generate a pool of taste bud progenitor
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the formation of endoderm derived taste sensory organs requires a pax9 dependent expansion of embryonic taste bud progenitor cells
PLOS Genetics, 2014Co-Authors: Ralf Kist, Michelle Watson, Moira Crosier, Max Robinson, Jennifer Fuchs, Julia Reichelt, Heiko PetersAbstract:In mammals, taste buds develop in different regions of the oral cavity. Small epithelial protrusions form fungiform Papillae on the ectoderm-derived dorsum of the tongue and contain one or few taste buds, while taste buds in the soft palate develop without distinct papilla structures. In contrast, the endoderm-derived circumvallate and foliate Papillae located at the back of the tongue contain a large number of taste buds. These taste buds cluster in deep epithelial trenches, which are generated by intercalating a period of epithelial growth between initial placode formation and conversion of epithelial cells into sensory cells. How epithelial trench formation is genetically regulated during development is largely unknown. Here we show that Pax9 acts upstream of Pax1 and Sox9 in the expanding taste progenitor field of the mouse circumvallate papilla. While a reduced number of taste buds develop in a growth-retarded circumvallate papilla of Pax1 mutant mice, its development arrests completely in Pax9-deficient mice. In addition, the Pax9 mutant circumvallate papilla trenches lack expression of K8 and Prox1 in the taste bud progenitor cells, and gradually differentiate into an epidermal-like epithelium. We also demonstrate that taste placodes of the soft palate develop through a Pax9-dependent induction. Unexpectedly, Pax9 is dispensable for patterning, morphogenesis and maintenance of taste buds that develop in ectoderm-derived fungiform Papillae. Collectively, our data reveal an endoderm-specific developmental program for the formation of taste buds and their associated papilla structures. In this pathway, Pax9 is essential to generate a pool of taste bud progenitors and to maintain their competence towards prosensory cell fate induction.
