<i>SOX10</i>-<i>Cre</i>-Labeled Cells Under the Tongue Epithelium Serve as Progenitors for Taste Bud Cells That Are Mainly Type III and Keratin 8-Low

Yu, Wenxin; Ishan, Mohamed; Yao, Yao; Stice, Steven L.; Liu, Hongxiang

doi:10.1089/scd.2020.0022

Cited by 10 publications

(16 citation statements)

References 42 publications

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“…Such a complete loss of taste papilla cells was consistently observed (Fig. 2F) in Alk3 cKO using another Cre driver, Sox10-Cre that exclusively marks neural crest-derived mesenchyme (Yu et al, 2020) (Supplemental Fig. 1).…”

Section: Mesenchyme-specific Knockout Of Alk3 But Not Alk2 Leads To A...mentioning

confidence: 54%

“…To understand the role of ALK3-mediated BMP (hereafter ALK3-BMP) signaling in the tongue mesenchyme, mesenchyme-specific knockout of Alk3 (Alk3 cKO) were generated using Wnt1-Cre (Jiang et al, 2000) and Sox10-Cre (Matsuoka et al, 2005) that largely labels the mesenchymal cells in the developing tongue (Liu et al, 2012, Thirumangalathu et al, 2009, Ishan et al, 2021, Yu et al, 2020. In Wnt1-Cre/Alk3 cKO tongues, Alk3 transcripts were significantly reduced in the mesenchyme (Fig.…”

Section: Mesenchyme-specific Knockout Of Alk3 But Not Alk2 Leads To A...mentioning

confidence: 99%

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Taste papilla cell differentiation requires tongue mesenchyme via ALK3-BMP signaling to regulate the production of secretory proteins

Ishan

Wang

Zhao

et al. 2023

Preprint

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Taste papillae are specialized organs each of which is comprised of an epithelial wall hosting taste buds and a core of mesenchymal tissue. In the present study, we report that during the early stages of embryonic development, bone morphogenetic protein (BMP) signaling mediated by type 1 receptor ALK3 in the tongue mesenchyme is required for the epithelial Wnt/β-catenin activity and taste papilla cell differentiation. Mesenchyme-specific knockout (cKO) of Alk3 using Wnt1-Cre and Sox10-Cre resulted in an absence of taste papillae at E12.0. Biochemical and cell differentiation analyses demonstrated that mesenchymal ALK3-BMP signaling governs the production of previously unappreciated secretory proteins, i.e., suppresses those that inhibiting and facilitates those promoting taste cell differentiation. Bulk RNA-Sequencing analysis revealed many more differentially expressed genes (DEGs) in the tongue epithelium than in the mesenchyme in Alk3 cKO vs control. Moreover, we detected a down-regulated epithelial Wnt/β-catenin signaling, and taste papilla development in the Alk3 cKO was rescued by GSK3β inhibitor LiCl, but not Wnt3a. Our findings demonstrate for the first time the requirement of tongue mesenchyme in taste papilla cell differentiation.

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Section: Mesenchyme-specific Knockout Of Alk3 But Not Alk2 Leads To A...mentioning

confidence: 54%

Section: Mesenchyme-specific Knockout Of Alk3 But Not Alk2 Leads To A...mentioning

confidence: 99%

Taste papilla cell differentiation requires tongue mesenchyme via ALK3-BMP signaling to regulate the production of secretory proteins

Ishan

Wang

Zhao

et al. 2023

Preprint

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“…To define the role of ALK3-BMP signaling in the tongue mesenchyme, a neural crest (NC)-derived mesenchyme-specific knockout of Alk3 ( Alk3 cKO ) was generated using Wnt1-Cre ( Jiang et al, 2000 ), which marks the NC cell lineage in the tongue mesenchyme extensively ( Thirumangalathu et al, 2009 ; Ishan et al, 2021 ; Yu et al, 2020 ; Liu et al, 2012a ). In Wnt1-Cre/Alk3 cKO tongues, Alk3 transcripts were significantly reduced in the mesenchyme ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To further confirm that the loss of taste papilla phenotype is indeed caused by the mesenchyme-specific deletion of Alk3 , another Cre driver, Sox10-Cre was used ( Yu et al, 2020 ; Matsuoka et al, 2005 ). Sox10-Cre -labeled cells were exclusively distributed in the tongue mesenchyme in serial sections of E12.0 Sox10-Cre/nTnG tongues ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Taste papilla cell differentiation requires the regulation of secretory protein production by ALK3-BMP signaling in the tongue mesenchyme

Ishan,

Wang,

Zhao

et al. 2023

Development

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Taste papillae are specialized organs each of which is comprised of an epithelial wall hosting taste buds and a core of mesenchymal tissue. In the present study, we report that during the early taste papilla development in mouse embryos, bone morphogenetic protein (BMP) signaling mediated by type 1 receptor ALK3 in the tongue mesenchyme is required for the epithelial Wnt/β-catenin activity and taste papilla differentiation. Mesenchyme-specific knockout (cKO) of Alk3 using Wnt1-Cre and Sox10-Cre resulted in an absence of taste papillae at E12.0. Biochemical and cell differentiation analyses demonstrated that mesenchymal ALK3-BMP signaling governs the production of previously unappreciated secretory proteins, i.e., suppresses those that inhibit and facilitates those promoting taste papilla differentiation. Bulk RNA-Sequencing analysis revealed many more differentially expressed genes (DEGs) in the tongue epithelium than in the mesenchyme in Alk3 cKO vs control. Moreover, we detected a down-regulated epithelial Wnt/β-catenin signaling and found that taste papilla development in the Alk3 cKO was rescued by GSK3β inhibitor LiCl, but not Wnt3a. Our findings demonstrate for the first time the requirement of tongue mesenchyme in taste papilla cell differentiation.

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“…The author interpreted this as suggesting a potentially important role for duct epithelium in taste bud generation. More recently, Yu et al (2020) used a Sox10-Cre reporter mouse strain in cell fate mapping experiments to demonstrate Sox10-Cre-labeled cells within taste buds in all three types of taste papillae. These authors found that Sox10 transcripts were absent from the taste epithelium, but present in subepithelial connective tissue and in secretory (acinar) and duct cells of von Ebner’s glands.…”

Section: Discussionmentioning

confidence: 99%

Lgr5⁺ductal cells of von Ebner’s glands are stem cells for turnover of posterior tongue taste buds

Harrison,

Downs,

Slepian

et al. 2024

Preprint

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Taste bud cells have a limited lifespan and must be continuously replaced along with the papilla epithelium in which they reside. Previous work has shown that expression of leucine-rich G protein-coupled receptor 5 (Lgr5), a Wnt pathway agonist, serves as a marker of adult stem/progenitor cells for taste buds located in posterior tongue (circumvallate and foliate), but not anterior tongue (fungiform), taste papillae. However, the specific location/niche of theLgr5-expressing cells supporting renewal and their phenotypic properties have not been fully explored. To address this the genesis and fate of Lgr5+cells were examined in developing and adult mice using genetic reporter strains. Evidence fromLgr5-lacZandLgr5-GFPmice shows that, whileLgr5is broadly expressed in epithelium of nascent circumvallate papillae and their trenches during embryonic development, it becomes concentrated within the ducts of adjacent von Ebner's salivary glands during the first postnatal week, co-incident with the appearance of differentiated taste buds. In posterior tongue taste papillae of adult animals, sites of highestLgr5expression are found in excretory ducts, restricted to the outer (basal) layer of the bi-layered excretory zone. These Lgr5+cells are immunoreactive for keratin 14, like cells in the basal layer of extragemmal taste epithelium, and for Sox9, a marker of exocrine gland duct cells. Lineage tracing experiments with anLgr5-EGFP-IRES-CreERT2;R26-mTmGreporter show that Lgr5+ductal cells become labeled one day following Cre induction, prior to the appearance of descendent cells in taste buds and extragemmal epithelium. These data support a role for Lgr5+ductal cells as stem cells and suggest that a cooperative interaction exists between posterior taste epithelium and its associated salivary glands in taste cell turnover.

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SOX10-Cre-Labeled Cells Under the Tongue Epithelium Serve as Progenitors for Taste Bud Cells That Are Mainly Type III and Keratin 8-Low

Cited by 10 publications

References 42 publications

Taste papilla cell differentiation requires tongue mesenchyme via ALK3-BMP signaling to regulate the production of secretory proteins

Taste papilla cell differentiation requires tongue mesenchyme via ALK3-BMP signaling to regulate the production of secretory proteins

Taste papilla cell differentiation requires the regulation of secretory protein production by ALK3-BMP signaling in the tongue mesenchyme

Lgr5⁺ductal cells of von Ebner’s glands are stem cells for turnover of posterior tongue taste buds

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SOX10-Cre-Labeled Cells Under the Tongue Epithelium Serve as Progenitors for Taste Bud Cells That Are Mainly Type III and Keratin 8-Low

Cited by 10 publications

References 42 publications

Taste papilla cell differentiation requires tongue mesenchyme via ALK3-BMP signaling to regulate the production of secretory proteins

Taste papilla cell differentiation requires tongue mesenchyme via ALK3-BMP signaling to regulate the production of secretory proteins

Taste papilla cell differentiation requires the regulation of secretory protein production by ALK3-BMP signaling in the tongue mesenchyme

Lgr5+ductal cells of von Ebner’s glands are stem cells for turnover of posterior tongue taste buds

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Lgr5⁺ductal cells of von Ebner’s glands are stem cells for turnover of posterior tongue taste buds