期刊
BONE
卷 155, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2021.116263
关键词
BMP; Regeneration; Gene regulation; Injury enhancer; Fin regeneration; Hair cell injury
资金
- National Institutes of Health [2T32GM00779038, NIH R35 NS111584, AR42236]
A small sequence that responds to evolutionarily conserved local signals in wounded tissues has been identified, potentially contributing to the reactivation of BMP after injury.
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.
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