The integrity of taste buds is intimately dependent on an intact gustatory innervation, yet the molecular nature of this dependency is unknown. Here we show differentiation of new taste bud cells, but not progenitor proliferation, is interrupted in mice treated with a Hedgehog (Hh) pathway inhibitor (HPI), and that gustatory nerves are a source of Shh for taste bud renewal. Additionally, epithelial taste precursor cells express Shh transiently, and are a local supply of Hh ligand supporting taste cell renewal. Taste buds are minimally affected when Shh is lost from either tissue source. However when both the epithelial and neural supply of Shh are removed, taste buds are virtually lost. We conclude Shh supplied by taste nerves and local taste epithelium act in concert to support continued taste bud differentiation. However, while neurally derived Shh is in part responsible for the dependence of taste cell renewal on gustatory innervation, neurotrophic support of taste buds likely involves a complex set of factors.
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