R-spondin substitutes for neuronal input for taste cell regeneration

R-spondin substitutes for neuronal input for taste cell regeneration


Like all cells, the 50 to 100 taste cells in the human taste bud age and lose their integrity over time. First shown more than a century ago, signals from distant, gustatory ganglion neurons tell adult taste stem cells when to differentiate and replenish taste buds; however, researchers have yet to determine exactly which neuron-supplied factors mediate the production of differentiated taste cells.

Taking advantage of a recently published RNAseq data set of mouse gustatory neurons, the authors use data mining and in situ hybridization to reveal that R-spondin-2—a member of the R-spondin family of proteins involved in Wnt signaling and stem cell differentiation—is predominantly expressed in gustatory neurons.

The authors demonstrate that R-spondin-2, the ligand of Lgr5 and its homologs Lgr4/6 and stem-cell-expressed E3 ligases Rnf43/Znrf3, is expressed in nodose-petrosal and geniculate ganglion neurons.

To support their findings, the authors use an in vivo mouse model to demonstrate that exogenous R-spondin promotes taste stem cell differentiation and taste tissue homeostasis in the absence of the neuronal signaling and that R-spondin is required to produce taste cells in ex vivo organoid cultures.

They also show that systemic delivery of R-spondin via adenovirus can promote generation of differentiated taste cells despite denervation. Thus, exogenous R-spondin can substitute for neuronal input for taste bud cell replenishment and taste bud maintenance.

The study argues that R-spondin-2 may be the unknown neuron-supplied factor that maintains taste cells throughout the human lifespan, as well as a potential treatment for patients who lose their sense of taste. 

https://www.pnas.org/content/118/2/e2001833118

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