Genetic Lineage Tracing in Taste Tissues Using Sox2-CreERT2 Strain

Ohmoto, Makoto; Ren, Wenwen; Nishiguchi, Yugo; Hirota, Junji; Jiang, Peihua; Matsumoto, Ichiro

doi:10.1093/chemse/bjx032

Cited by 25 publications

(35 citation statements)

References 36 publications

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“…Notably, SOX2-GFP reporter expression recapitulated SOX2 protein expression in adult tongue (see Fig 3A and Suzuki, 2008;Okubo et al, 2009;Ohmoto et al, 2017).…”

Section: Resultsmentioning

confidence: 75%

“…2F arrows). SOX2 + basal keratinocytes outside of taste buds are taste bud stem cells (Ohmoto et al, 2017), but it is not known if perigemmal SOX2 hi and/or FFP wall SOX2 mid cells function in this role.…”

Section: Resultsmentioning

confidence: 99%

“…In the adult tongue, SOX2 is expressed at low levels by K14 + cells, and Sox2 genetic lineage tracing confirms that SOX2 + basal keratinocytes also function as bipotential stem cells for taste and non-taste lingual epithelium (Ohmoto et al, 2017). Further, SOX2 is robustly expressed in perigemmal K14 + taste bud progenitors, basal cells within taste buds and in a subset of mature taste receptor cells (Okubo et al, 2006;Suzuki, 2008;Ohmoto et al, 2017), suggesting that SOX2 may be key to proper taste cell differentiation from progenitors. Interestingly, overexpression of SHH in K14 + progenitors leads to formation of ectopic taste buds, which are associated with increased SOX2 expression in epithelial cells surrounding and within ectopic buds (Castillo et al, 2014).…”

Section: Introductionmentioning

confidence: 83%

“…In the adult tongue, SOX2 is highly expressed in perigemmal cells and in a subset of intragemmal taste bud cells, whereas SOX2 expression is low in the basal keratinocytes of the non-taste epithelium (Okubo et al, 2006;Suzuki, 2008;Okubo et al, 2009;Ohmoto et al, 2017). In adult mice, after transection of the glossopharyngeal nerve innervating the posterior circumvallate taste papilla, taste buds disappear, as does SOX2 expression in taste progenitors and taste buds.…”

Section: Discussionmentioning

confidence: 99%

“…The importance of SOX2 during embryonic taste development was first demonstrated by failure of Sox2 hypomorphic mutants to generate FF taste buds (Okubo et al, 2006). In the adult tongue, SOX2 is expressed at low levels by K14 + cells, and Sox2 genetic lineage tracing confirms that SOX2 + basal keratinocytes also function as bipotential stem cells for taste and non-taste lingual epithelium (Ohmoto et al, 2017). Further, SOX2 is robustly expressed in perigemmal K14 + taste bud progenitors, basal cells within taste buds and in a subset of mature taste receptor cells (Okubo et al, 2006;Suzuki, 2008;Ohmoto et al, 2017), suggesting that SOX2 may be key to proper taste cell differentiation from progenitors.…”

Section: Introductionmentioning

confidence: 99%

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SOX2 Regulation by Hedgehog Signaling Controls Adult Lingual Epithelium Homeostasis

Castillo-Azofeifa

Seidel

Gross

et al. 2018

Preprint

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The adult tongue epithelium is continuously renewed from epithelial progenitor cells, and this process relies on intact Hedgehog (HH) signaling. In mice, inhibition of the HH pathway using Smoothened antagonists (HH pathway inhibitors or HPIs) leads to taste bud loss over a span of several weeks. Previously, we demonstrated that overexpression of Sonic Hedgehog (SHH) in lingual epithelial progenitors induces formation of ectopic taste buds accompanied by locally increased SOX2 expression, consistent with the hypothesis that taste bud differentiation depends on SOX2 downstream of HH. To test this idea, we inhibited HH signaling by treating SOX2-GFP mice with HPI and found a rapid and drastic decline in SOX2-GFP expression in taste progenitors and taste buds. Using a conditional Cre-lox system to delete Sox2, we found that loss of SOX2 blocks differentiation of both taste buds and non-taste epithelium that comprises the majority of the tongue surface; progenitor cells increase in number at the expense of differentiated taste cells and lingual keratinocytes. In contrast to the normal pattern of basally restricted proliferation, dividing cells are overabundant, disorganized and present in suprabasal epithelial layers in Sox2 deleted tongues. Additionally, SOX2 loss in taste progenitors leads non-cell autonomously to rapid loss of taste bud cells via apoptosis, dramatically shortening taste cell lifespans. Finally, when Sox2 is conditionally deleted in mice with constitutive overexpression of SHH, ectopic taste buds fail to form and endogenous taste buds disappear; instead, robust hyperproliferation takes over the entire lingual epithelium. In sum, our experiments suggest that SOX2 functions downstream of HH signaling to regulate lingual epithelium homeostasis.All rights reserved. No reuse allowed without permission.

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“…Notably, SOX2-GFP reporter expression recapitulated SOX2 protein expression in adult tongue (see Fig 3A and Suzuki, 2008;Okubo et al, 2009;Ohmoto et al, 2017).…”

Section: Resultsmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

SOX2 Regulation by Hedgehog Signaling Controls Adult Lingual Epithelium Homeostasis

Castillo-Azofeifa

Seidel

Gross

et al. 2018

Preprint

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The sense of taste: Development, regeneration, and dysfunction

Barlow

2021

WIREs Mechanisms of Disease

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Gustation or the sense of taste is a primary sense, which functions as a gatekeeper for substances that enter the body. Animals, including humans, ingest foods that contain appetitive taste stimuli, including those that have sweet, moderately salty and umami (glutamate) components, and tend to avoid bitter‐tasting items, as many bitter compounds are toxic. Taste is mediated by clusters of heterogeneous taste receptors cells (TRCs) organized as taste buds on the tongue, and these convey taste information from the oral cavity to higher order brain centers via the gustatory sensory neurons of the seventh and ninth cranial ganglia. One remarkable aspect of taste is that taste perception is mostly uninterrupted throughout life yet TRCs within buds are constantly renewed; every 1–2 months all taste cells have been steadily replaced. In the past decades we have learned a substantial amount about the cellular and molecular regulation of taste bud cell renewal, and how taste buds are initially established during embryogenesis. Here I review more recent findings pertaining to taste development and regeneration, as well as discuss potential mechanisms underlying taste dysfunction that often occurs with disease or its treatment. This article is categorized under: Infectious Diseases > Stem Cells and Development Cancer > Stem Cells and Development Neurological Diseases > Stem Cells and Development

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