Limits...
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

Effects of Larp7 knockdown on cardiac structure and function. (A) Larp7-targeting morpholinos [either splice blocking (SB) or translation blocking (TB)] resulted in normal heart development, here shown in vivo (left hand panel) and following H&E staining (right hand panel). Ventricular diastolic area (B) and ejection fraction (C) in Larp7-knockdown embryos were similar to controls (Larp7 mismatch morpholino). A mild dilatation of the atrium (D) was observed in Larp7-knockdown (TB and SB Larp7-Mo) embryos. Larp7 mRNA (E) and protein (F) were significantly reduced at 48 and 96 hpf. Larp7-Mo-TB (larp7 Mo) injection caused increased phosphorylation of Ser2 in the RNA polymerase II C-terminal domain (P-Ser2 CTD), suggesting an upregulation of Cdk9 activity. n=3 experiments, *P<0.05, **P<0.01, ***P<0.001, two-way ANOVA followed by Bonferroni's post-hoc test. Means±s.e.m. are shown in B, C, D and E.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4696495&req=5

JCS175018F4: Effects of Larp7 knockdown on cardiac structure and function. (A) Larp7-targeting morpholinos [either splice blocking (SB) or translation blocking (TB)] resulted in normal heart development, here shown in vivo (left hand panel) and following H&E staining (right hand panel). Ventricular diastolic area (B) and ejection fraction (C) in Larp7-knockdown embryos were similar to controls (Larp7 mismatch morpholino). A mild dilatation of the atrium (D) was observed in Larp7-knockdown (TB and SB Larp7-Mo) embryos. Larp7 mRNA (E) and protein (F) were significantly reduced at 48 and 96 hpf. Larp7-Mo-TB (larp7 Mo) injection caused increased phosphorylation of Ser2 in the RNA polymerase II C-terminal domain (P-Ser2 CTD), suggesting an upregulation of Cdk9 activity. n=3 experiments, *P<0.05, **P<0.01, ***P<0.001, two-way ANOVA followed by Bonferroni's post-hoc test. Means±s.e.m. are shown in B, C, D and E.

Mentions: Larvae that had been injected with a morpholino blocking Larp7 splicing or translation (Larp7-Mo-SB and Larp7-Mo-TB, respectively) displayed similar rates of survival at 120 hpf to Larp7-mismatch-injected controls (90%) (Fig. S1C) with mild structural and cardiac abnormalities (see Fig. 4A; Fig. S3). Ventricle diastolic area and the ejection fraction were not different between the two groups (Fig. 4B,C), whereas atrial diastolic area was significantly greater in the hearts of embryos that had been injected with the Larp7 morpholinos compared to controls (Fig. 4D). Larp7-Mo-SB-injected larvae had a significant reduction in larp7 mRNA by approximately 40% (Fig. 4E) and a reduction in Larp7 protein by 70% (Fig. 4E,F) compared to controls. Larp7-Mo-TB-injected larvae showed an increase in phosphorylation of Ser2 on RNA polymerase II compared to mismatch-treated controls (Fig. 4F), consistent with activation of Cdk9.Fig. 4.


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)

Effects of Larp7 knockdown on cardiac structure and function. (A) Larp7-targeting morpholinos [either splice blocking (SB) or translation blocking (TB)] resulted in normal heart development, here shown in vivo (left hand panel) and following H&E staining (right hand panel). Ventricular diastolic area (B) and ejection fraction (C) in Larp7-knockdown embryos were similar to controls (Larp7 mismatch morpholino). A mild dilatation of the atrium (D) was observed in Larp7-knockdown (TB and SB Larp7-Mo) embryos. Larp7 mRNA (E) and protein (F) were significantly reduced at 48 and 96 hpf. Larp7-Mo-TB (larp7 Mo) injection caused increased phosphorylation of Ser2 in the RNA polymerase II C-terminal domain (P-Ser2 CTD), suggesting an upregulation of Cdk9 activity. n=3 experiments, *P<0.05, **P<0.01, ***P<0.001, two-way ANOVA followed by Bonferroni's post-hoc test. Means±s.e.m. are shown in B, C, D and E.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696495&req=5

JCS175018F4: Effects of Larp7 knockdown on cardiac structure and function. (A) Larp7-targeting morpholinos [either splice blocking (SB) or translation blocking (TB)] resulted in normal heart development, here shown in vivo (left hand panel) and following H&E staining (right hand panel). Ventricular diastolic area (B) and ejection fraction (C) in Larp7-knockdown embryos were similar to controls (Larp7 mismatch morpholino). A mild dilatation of the atrium (D) was observed in Larp7-knockdown (TB and SB Larp7-Mo) embryos. Larp7 mRNA (E) and protein (F) were significantly reduced at 48 and 96 hpf. Larp7-Mo-TB (larp7 Mo) injection caused increased phosphorylation of Ser2 in the RNA polymerase II C-terminal domain (P-Ser2 CTD), suggesting an upregulation of Cdk9 activity. n=3 experiments, *P<0.05, **P<0.01, ***P<0.001, two-way ANOVA followed by Bonferroni's post-hoc test. Means±s.e.m. are shown in B, C, D and E.
Mentions: Larvae that had been injected with a morpholino blocking Larp7 splicing or translation (Larp7-Mo-SB and Larp7-Mo-TB, respectively) displayed similar rates of survival at 120 hpf to Larp7-mismatch-injected controls (90%) (Fig. S1C) with mild structural and cardiac abnormalities (see Fig. 4A; Fig. S3). Ventricle diastolic area and the ejection fraction were not different between the two groups (Fig. 4B,C), whereas atrial diastolic area was significantly greater in the hearts of embryos that had been injected with the Larp7 morpholinos compared to controls (Fig. 4D). Larp7-Mo-SB-injected larvae had a significant reduction in larp7 mRNA by approximately 40% (Fig. 4E) and a reduction in Larp7 protein by 70% (Fig. 4E,F) compared to controls. Larp7-Mo-TB-injected larvae showed an increase in phosphorylation of Ser2 on RNA polymerase II compared to mismatch-treated controls (Fig. 4F), consistent with activation of Cdk9.Fig. 4.

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