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Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):E200-E209. doi: 10.1073/pnas.1719109115. Epub 2017 Dec 26.

Neuronal delivery of Hedgehog directs spatial patterning of taste organ regeneration.

Author information

1
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305; wjlu@stanford.edu pbeachy@stanford.edu.
2
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305.
3
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
4
Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305.
5
Department of Biology, Stanford University, Stanford, CA 94305.
6
Department of Developmental Biology, Stanford University, Stanford, CA 94305.
7
Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.

Abstract

How organs maintain and restore functional integrity during ordinary tissue turnover or following injury represents a central biological problem. The maintenance of taste sensory organs in the tongue was shown 140 years ago to depend on innervation from distant ganglion neurons, but the underlying mechanism has remained unknown. Here, we show that Sonic hedgehog (Shh), which encodes a secreted protein signal, is expressed in these sensory neurons, and that experimental ablation of neuronal Shh expression causes loss of taste receptor cells (TRCs). TRCs are also lost upon pharmacologic blockade of Hedgehog pathway response, accounting for the loss of taste sensation experienced by cancer patients undergoing Hedgehog inhibitor treatment. We find that TRC regeneration following such pharmacologic ablation requires neuronal expression of Shh and can be substantially enhanced by pharmacologic activation of Hedgehog response. Such pharmacologic enhancement of Hedgehog response, however, results in additional TRC formation at many ectopic sites, unlike the site-restricted regeneration specified by the projection pattern of Shh-expressing neurons. Stable regeneration of TRCs thus requires neuronal Shh, illustrating the principle that neuronal delivery of cues such as the Shh signal can pattern distant cellular responses to assure functional integrity during tissue maintenance and regeneration.

KEYWORDS:

Hedgehog signaling; genetics; neurobiology; regeneration; taste

PMID:
29279401
PMCID:
PMC5777079
DOI:
10.1073/pnas.1719109115
[Indexed for MEDLINE]
Free PMC Article

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