Characterization of mouse Bmp5 regulatory injury element in zebrafish wound models

Bone. 2022 Feb:155:116263. doi: 10.1016/j.bone.2021.116263. Epub 2021 Nov 23.

Abstract

Many key signaling molecules used to build tissues during embryonic development are re-activated at injury sites to stimulate tissue regeneration and repair. Bone morphogenetic proteins provide a classic example, but the mechanisms that lead to reactivation of BMPs following injury are still unknown. Previous studies have mapped a large "injury response element" (IRE) in the mouse Bmp5 gene that drives gene expression following bone fractures and other types of injury. Here we show that the large mouse IRE region is also activated in both zebrafish tail resection and mechanosensory hair cell injury models. Using the ability to test multiple constructs and image temporal and spatial dynamics following injury responses, we have narrowed the original size of the mouse IRE region by over 100 fold and identified a small 142 bp minimal enhancer that is rapidly induced in both mesenchymal and epithelial tissues after injury. These studies identify a small sequence that responds to evolutionarily conserved local signals in wounded tissues and suggest candidate pathways that contribute to BMP reactivation after injury.

Keywords: BMP; Fin regeneration; Gene regulation; Hair cell injury; Injury enhancer; Regeneration.

Publication types

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

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins* / metabolism
  • Embryonic Development
  • Mice
  • Regulatory Sequences, Nucleic Acid
  • Signal Transduction
  • Zebrafish* / genetics

Substances

  • Bone Morphogenetic Proteins