Reciprocal signals between nerve and epithelium: how do neurons talk with epithelial cells?

Most epithelium tissues continuously undergo self-renewal through proliferation and differentiation of epithelial stem cells (known as homeostasis), within a specialized stem cell niche. In highly innervated epithelium, peripheral nerves compose perineural niche and support stem cell homeostasis by releasing a variety of neurotransmitters, hormones, and growth factors and supplying trophic factors to the stem cells. Emerging evidence has shown that both sensory and motor nerves can regulate the fate of epithelial stem cells, thus influencing epithelium homeostasis. Understanding the mechanism of crosstalk between epithelial stem cells and neurons will reveal the important role of the perineural niche in physiological and pathological conditions. Herein, we review recent discoveries of the perineural niche in epithelium mainly in tissue homeostasis, with a limited touch in wound repair and pathogenesis.