期刊
DEVELOPMENTAL CELL
卷 48, 期 6, 页码 853-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2019.01.001
关键词
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资金
- American Heart Association (AHA)
- National Science Foundation
- AHA
- Swiss National Science Foundation
- National Institutes of Health (NIH)
- NIH [R01 HL081674, R01 GM074057, R01 HL136182, R01 HL131319]
- March of Dimes
- Fondation Leducq
Attaining proper organ size during development and regeneration hinges on the activity of mitogenic factors. Here, we performed a large-scale chemical screen in embryonic zebrafish to identify cardiomyocyte mitogens. Although commonly considered antiproliferative, vitamin D analogs like alfacalcidol had rapid, potent mitogenic effects on embryonic and adult cardiomyocytes in vivo. Moreover, pharmacologic or genetic manipulation of vitamin D signaling controlled proliferation in multiple adult cell types and dictated growth rates in embryonic and juvenile zebrafish. Tissue-specific modulation of vitamin D receptor (VDR) signaling had organ-restricted effects, with cardiac VDR activation causing cardiomegaly. Alfacalcidol enhanced the regenerative response of injured zebrafish hearts, whereas VDR blockade inhibited regeneration. Alfacalcidol activated cardiac expression of genes associated with ErbB2 signaling, while ErbB2 inhibition blunted its effects on cell proliferation. Our findings identify vitamin D as mitogenic for cardiomyocytes and other cell types in zebrafish and indicate a mechanism to regulate organ size and regeneration.
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