PUBLICATION

Vitamin D Stimulates Cardiomyocyte Proliferation and Controls Organ Size and Regeneration in Zebrafish

Authors
Han, Y., Chen, A., Umansky, K.B., Oonk, K.A., Choi, W.Y., Dickson, A.L., Ou, J., Cigliola, V., Yifa, O., Cao, J., Tornini, V.A., Cox, B.D., Tzahor, E., Poss, K.D.
ID
ZDB-PUB-190205-2
Date
2019
Source
Developmental Cell   48(6): 853-863.e5 (Journal)
Registered Authors
Cao, Jingli, Chen, Anzhi, Choi, Wen-Yee, Cigliola, Valentina, Cox, Ben, Dickson, Amy, Han, Yanchao, Ou, Jianhong, Poss, Kenneth D., Tornini, Valerie A.
Keywords
ErbB2 signaling, cardiomyocyte, cell proliferation, chemical screen, heart, mitogen, regeneration, size control, vitamin D, zebrafish
Datasets
GEO:GSE112826
MeSH Terms
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Organ Size/drug effects
  • Heart/anatomy & histology*
  • Heart/drug effects
  • Heart/physiology*
  • Vitamin D/pharmacology*
  • Mitogens/pharmacology
  • Signal Transduction/drug effects
  • Cell Proliferation/drug effects
  • Cell Cycle/drug effects
  • Animals
  • Organ Specificity
  • Zebrafish/anatomy & histology*
  • Zebrafish/embryology
  • Zebrafish/physiology*
  • Myocytes, Cardiac/cytology*
  • Myocytes, Cardiac/drug effects
  • Myocytes, Cardiac/metabolism
  • Regeneration/drug effects*
  • Zebrafish Proteins/metabolism
(all 21)
PubMed
30713073 Full text @ Dev. Cell
Abstract
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 anti-proliferative, 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.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTchemical treatment by environment: alfacalcidolProtruding-mouth
WTchemical treatment by environment: alfacalcidolProtruding-mouth
WTchemical treatment by environment: alfacalcidolProtruding-mouth to Day 4
WTchemical treatment by environment: alfacalcidolDay 4
WTchemical treatment by environment: alfacalcidolDay 4
WTchemical treatment by environment: alfacalcidolAdult
WTchemical treatment by environment: alfacalcidolAdult
WTchemical treatment by injection: alfacalcidolAdult
WTchemical treatment by injection: alfacalcidolAdult
WTchemical treatment by injection: tyrphostin AG 1478, chemical treatment by injection: alfacalcidolAdult
1 - 10 of 60
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mu122TgTransgenic Insertion
    pd10TgTransgenic Insertion
      pd36TgTransgenic Insertion
        pd57TgTransgenic Insertion
          pd58TgTransgenic Insertion
            pd115TgTransgenic Insertion
              pd254TgTransgenic Insertion
                pd255TgTransgenic Insertion
                  pd270TgTransgenic Insertion
                    pd271TgTransgenic Insertion
                      1 - 10 of 23
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      cyp24a1TALEN1-cyp24a1TALEN
                      vdraCRISPR2-vdraCRISPR
                      vdraCRISPR3-vdraCRISPR
                      vdrbCRISPR1-vdrbCRISPR
                      vdrbCRISPR2-vdrbCRISPR
                      1 - 5 of 5
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                      Fish
                      Fish
                      cyp24a1pd272Tg/+
                      cyp24a1pd272Tg/+; pd273Tg/+
                      cyp24a1pd272Tg/+; pd276Tg/+
                      cyp24a1pd272Tg/+; pd301Tg/+
                      cyp24a1pd272Tg/+; pd302Tg/+
                      pd57Tg/+; pd58Tg/+
                      pd273Tg/+
                      pd274Tg/+
                      pd276Tg/+
                      pd276Tg/+; pd57Tg/+; pd58Tg/+
                      1 - 10 of 18
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                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CreEFGCre
                      DipToxEFGDipTox
                      DsRedEFGDsRed
                      ECFPEFGECFP
                      EGFPEFGEGFP
                      GFPEFGGFP
                      mAGFPEFGmAGFP
                      mCherryEFGmCherry
                      mKOFP2EFGmKOFP2
                      TagBFPEFGTagBFP
                      1 - 10 of 11
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                      Mapping
                      No data available
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                      Citation
                      Han, Y., Chen, A., Umansky, K.B., Oonk, K.A., Choi, W.Y., Dickson, A.L., Ou, J., Cigliola, V., Yifa, O., Cao, J., Tornini, V.A., Cox, B.D., Tzahor, E., Poss, K.D. (2019) Vitamin D Stimulates Cardiomyocyte Proliferation and Controls Organ Size and Regeneration in Zebrafish. Developmental Cell. 48(6):853-863.e5.