Polycomb Repressive Complex 1 Controls Maintenance of Fungiform Papillae by Repressing Sonic Hedgehog Expression

Cell Rep. 2019 Jul 2;28(1):257-266.e5. doi: 10.1016/j.celrep.2019.06.011.

Abstract

How tissue patterns are formed and maintained are fundamental questions. The murine tongue epithelium, a paradigm for tissue patterning, consists of an array of specialized fungiform papillae structures that harbor taste cells. The formation of fungiform papillae is preceded by pronounced spatial changes in gene expression, in which taste cell genes such as Shh, initially diffused in lingual epithelial progenitors, become restricted to taste cells when their specification progresses. However, the requirement of spatial restriction of taste cell gene expression for patterning and formation of fungiform papillae is unknown. Here, we show that a chromatin regulator, Polycomb repressive complex (PRC) 1, is required for proper maintenance of fungiform papillae by repressing Shh and preventing ectopic SHH signaling in non-taste cells. Ablation of SHH signaling in PRC1-null non-taste cells rescues the maintenance of taste cells. Altogether, our studies exemplify how epigenetic regulation establishes spatial gene expression patterns necessary for specialized niche structures.

Keywords: PRC1; Polycomb; Sonic Hedgehog; filiform papillae; fungiform papillae.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Cell Cycle / genetics
  • Chromatin Immunoprecipitation
  • Chromatin Immunoprecipitation Sequencing
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Epigenesis, Genetic
  • Epithelium / metabolism
  • Epithelium / ultrastructure
  • Gene Expression Regulation, Developmental / genetics
  • Gene Ontology
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Scanning
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 1 / metabolism*
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism
  • RNA-Seq
  • Signal Transduction / genetics
  • Taste Buds / growth & development
  • Taste Buds / metabolism*
  • Taste Buds / ultrastructure
  • Tongue / growth & development
  • Tongue / metabolism*
  • Tongue / physiology

Substances

  • Cdkn2a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • Hedgehog Proteins
  • Shh protein, mouse
  • Polycomb Repressive Complex 2
  • Polycomb Repressive Complex 1
  • Ring1 protein, mouse