scholarly journals SOX2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis

Development ◽  
2018 ◽  
Vol 145 (14) ◽  
pp. dev164889 ◽  
Author(s):  
David Castillo-Azofeifa ◽  
Kerstin Seidel ◽  
Lauren Gross ◽  
Erin J. Golden ◽  
Belkis Jacquez ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Lingual Epithelium

scholarly journals Hedgehog Signaling Regulates Taste Organs and Oral Sensation: Distinctive Roles in the Epithelium, Stroma, and Innervation

2019 ◽  
Vol 20 (6) ◽  
pp. 1341 ◽  
Author(s):  
Charlotte Mistretta ◽  
Archana Kumari
Keyword(s):  
Hedgehog Signaling ◽  
Nerve Fibers ◽  
Taste Buds ◽  
Drug Discontinuation ◽  
Taste Sensation ◽  
Lingual Epithelium ◽  
Basic Biology ◽  
Hh Signaling ◽  
Ganglion Neurons ◽  
Tissue Compartments

The Hedgehog (Hh) pathway has regulatory roles in maintaining and restoring lingual taste organs, the papillae and taste buds, and taste sensation. Taste buds and taste nerve responses are eliminated if Hh signaling is genetically suppressed or pharmacologically inhibited, but regeneration can occur if signaling is reactivated within the lingual epithelium. Whereas Hh pathway disruption alters taste sensation, tactile and cold responses remain intact, indicating that Hh signaling is modality-specific in regulation of tongue sensation. However, although Hh regulation is essential in taste, the basic biology of pathway controls is not fully understood. With recent demonstrations that sonic hedgehog (Shh) is within both taste buds and the innervating ganglion neurons/nerve fibers, it is compelling to consider Hh signaling throughout the tongue and taste organ cell and tissue compartments. Distinctive signaling centers and niches are reviewed in taste papilla epithelium, taste buds, basal lamina, fibroblasts and lamellipodia, lingual nerves, and sensory ganglia. Several new roles for the innervation in lingual Hh signaling are proposed. Hh signaling within the lingual epithelium and an intact innervation each is necessary, but only together are sufficient to sustain and restore taste buds. Importantly, patients who use Hh pathway inhibiting drugs confront an altered chemosensory world with loss of taste buds and taste responses, intact lingual touch and cold sensation, and taste recovery after drug discontinuation.

scholarly journals SOX2 Regulation by Hedgehog Signaling Controls Adult Lingual Epithelium Homeostasis

2018 ◽  
Author(s):  
David Castillo-Azofeifa ◽  
Kerstin Seidel ◽  
Lauren Gross ◽  
Belkis Jacquez ◽  
Ophir D. Klein ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Hedgehog Signaling ◽  
Taste Buds ◽  
Taste Bud ◽  
Lingual Epithelium ◽  
Sox2 Expression ◽  
Dividing Cells ◽  
Constitutive Overexpression ◽  
Hh Signaling ◽  
Epithelial Layers

AbstractThe 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.

667: Sonic Hedgehog Signaling Plays a Pivotal Role in the Vicious Cycle between Human Prostate Cancer and Normal/Benign but not Cancer Associated Human Prostate Stromal Cells

2007 ◽  
Vol 177 (4S) ◽  
pp. 224-224
Author(s):  
Katsumi Shigemura ◽  
Wen-Chin Haung ◽  
Fray F. Marshall ◽  
Haiyen E. Zhau ◽  
Leland W.K. Chung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Sonic Hedgehog ◽  
Stromal Cells ◽  
Hedgehog Signaling ◽  
Pivotal Role ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Vicious Cycle ◽  
Sonic Hedgehog Signaling

Hedgehog signaling inhibitors isolated from myxomycetes and a Solanaceae plant

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
M Ishibashi ◽  
T Hosoya ◽  
C Tateno ◽  
MA Arai
Keyword(s):  
Hedgehog Signaling ◽  
Signaling Inhibitors
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