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CDK9 and its repressor LARP7 modulate cardiomyocyte proliferation and response to injury in the zebrafish heart.

Matrone G, Wilson KS, Maqsood S, Mullins JJ, Tucker CS, Denvir MA - J. Cell. Sci. (2015)

Bottom Line: Cdk9 expression and activity were inhibited in the zebrafish (Danio rerio) embryo.We show that dephosphorylation of residue Ser2 on the C-terminal domain of RNA polymerase II is associated with impaired cardiac structure and function, and cardiomyocyte proliferation and also results in impaired functional recovery following cardiac laser injury.Larp7 knockdown rescued the structural and functional phenotype associated with knockdown of Cdk9.

View Article: PubMed Central - PubMed

Affiliation: British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Methodist Hospital Research Institute, Houston, TX 77030, USA.

No MeSH data available.


Related in: MedlinePlus

Rescue of the Cdk9-knockdown phenotype using capped cdk9 mRNA or Larp7-Mo-SB. (A–C) Survival and phenotype score in embryos treated with CDK9-Mo-SB (Cdk9-Mo), LARP7-Mo-SB (Larp7-Mo), CDK9-Mo-SB+cdk9 mRNA, Cdk9-Mo-SB+Larp7-Mo-SB assessed independently during the first 120 hpf (n=3 experiments, n>50 embryos per group). (D) Effects of rescuing the Cdk9-knockdown phenotype (cdk9 mRNA or Larp7-Mo-SB) on recovery of the cardiac function after laser injury (N=3, n=20–30 embryos per experiment). Two-way ANOVA and Bonferroni post-hoc test; ns, non-significant; *P<0.05, **P<0.01 and ***P<0.001. Means±s.e.m. are shown in B, C and D.
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JCS175018F8: Rescue of the Cdk9-knockdown phenotype using capped cdk9 mRNA or Larp7-Mo-SB. (A–C) Survival and phenotype score in embryos treated with CDK9-Mo-SB (Cdk9-Mo), LARP7-Mo-SB (Larp7-Mo), CDK9-Mo-SB+cdk9 mRNA, Cdk9-Mo-SB+Larp7-Mo-SB assessed independently during the first 120 hpf (n=3 experiments, n>50 embryos per group). (D) Effects of rescuing the Cdk9-knockdown phenotype (cdk9 mRNA or Larp7-Mo-SB) on recovery of the cardiac function after laser injury (N=3, n=20–30 embryos per experiment). Two-way ANOVA and Bonferroni post-hoc test; ns, non-significant; *P<0.05, **P<0.01 and ***P<0.001. Means±s.e.m. are shown in B, C and D.

Mentions: Co-injection of larvae with Cdk9-Mo-SB and Larp7-Mo-SB significantly attenuated the morphological abnormalities observed with Cdk9-Mo-SB alone, with fewer embryos displaying body axis and cardiac abnormalities (Fig. 8A–C). Co-injection of Cdk9-Mo-SB and cdk9 RNA also significantly rescued the morphological phenotype observed with Cdk9-Mo-SB alone (Fig. 8A–C). There were significantly fewer larvae with small heads, curved tails, string-like hearts and with a lack of tail blood flow. Although the rescue with cdk9 capped RNA did not completely restore the phenotype to normal, we observed a substantial improvement in the structural and functional cardiac phenotype (Fig. 8C).Fig. 8.


CDK9 and its repressor LARP7 modulate cardiomyocyte proliferation and response to injury in the zebrafish heart.

Matrone G, Wilson KS, Maqsood S, Mullins JJ, Tucker CS, Denvir MA - J. Cell. Sci. (2015)

Rescue of the Cdk9-knockdown phenotype using capped cdk9 mRNA or Larp7-Mo-SB. (A–C) Survival and phenotype score in embryos treated with CDK9-Mo-SB (Cdk9-Mo), LARP7-Mo-SB (Larp7-Mo), CDK9-Mo-SB+cdk9 mRNA, Cdk9-Mo-SB+Larp7-Mo-SB assessed independently during the first 120 hpf (n=3 experiments, n>50 embryos per group). (D) Effects of rescuing the Cdk9-knockdown phenotype (cdk9 mRNA or Larp7-Mo-SB) on recovery of the cardiac function after laser injury (N=3, n=20–30 embryos per experiment). Two-way ANOVA and Bonferroni post-hoc test; ns, non-significant; *P<0.05, **P<0.01 and ***P<0.001. Means±s.e.m. are shown in B, C and D.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4696495&req=5

JCS175018F8: Rescue of the Cdk9-knockdown phenotype using capped cdk9 mRNA or Larp7-Mo-SB. (A–C) Survival and phenotype score in embryos treated with CDK9-Mo-SB (Cdk9-Mo), LARP7-Mo-SB (Larp7-Mo), CDK9-Mo-SB+cdk9 mRNA, Cdk9-Mo-SB+Larp7-Mo-SB assessed independently during the first 120 hpf (n=3 experiments, n>50 embryos per group). (D) Effects of rescuing the Cdk9-knockdown phenotype (cdk9 mRNA or Larp7-Mo-SB) on recovery of the cardiac function after laser injury (N=3, n=20–30 embryos per experiment). Two-way ANOVA and Bonferroni post-hoc test; ns, non-significant; *P<0.05, **P<0.01 and ***P<0.001. Means±s.e.m. are shown in B, C and D.
Mentions: Co-injection of larvae with Cdk9-Mo-SB and Larp7-Mo-SB significantly attenuated the morphological abnormalities observed with Cdk9-Mo-SB alone, with fewer embryos displaying body axis and cardiac abnormalities (Fig. 8A–C). Co-injection of Cdk9-Mo-SB and cdk9 RNA also significantly rescued the morphological phenotype observed with Cdk9-Mo-SB alone (Fig. 8A–C). There were significantly fewer larvae with small heads, curved tails, string-like hearts and with a lack of tail blood flow. Although the rescue with cdk9 capped RNA did not completely restore the phenotype to normal, we observed a substantial improvement in the structural and functional cardiac phenotype (Fig. 8C).Fig. 8.

Bottom Line: Cdk9 expression and activity were inhibited in the zebrafish (Danio rerio) embryo.We show that dephosphorylation of residue Ser2 on the C-terminal domain of RNA polymerase II is associated with impaired cardiac structure and function, and cardiomyocyte proliferation and also results in impaired functional recovery following cardiac laser injury.Larp7 knockdown rescued the structural and functional phenotype associated with knockdown of Cdk9.

View Article: PubMed Central - PubMed

Affiliation: British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Methodist Hospital Research Institute, Houston, TX 77030, USA.

No MeSH data available.


Related in: MedlinePlus