Abstract 142: Role of CK2α in Heart Tube Proliferation
Congenital heart disease (CHD) groups a number of structural malformations of the heart and associated blood vessels present at birth. CHD is the most common birth defect, arise from defective cardiogenesis, and can be due to genetic and/or environmental factors that affect cellular processes such as proliferation during heart formation. The highly conserved serine-threonine kinase, CK2α, has been implicated in proliferative processes, including cancer, and it is a target of environmental toxins. To test whether CK2α plays a role in cardiogenesis, we used a CK2α deficient mouse. CK2α-/- mice die around embryonic day (E)11 and showed dysmorphic outflow tracts (OFT), hypoplastic right ventricles (RV) and poorly developed ventricular trabeculations. These defects, the probable cause of the lethality, could be due to deficient proliferation. Thus, we tested whether reduced CK2α expression leads to proliferative signal defects during cardiogenesis.
We used three or more pairs of somite-matched wild-type and CK2α-/- embryos for the analysis of proteins by immunofluorescence and immunoblot, and of transcript expression by RT-qPCR and in situ hybridization. At E9.5 and E10.5, the number of Isl1+ cells in the OFT and the levels of Isl1 transcript in the heart of CK2α-/- embryos was no different from wild-type. These data suggest that the mechanism underlying the OFT and RV defects is different from progenitor incorporation defects. CK2α deficient hearts expressed pan-cardiac gene and protein markers normally at E9.5 and E10.5; and apoptosis was not affected, indicating that the heart malformations may be due to proliferative defects. Indeed, mitotic rates were decreased throughout the heart in CK2α mutants compared to wild-type embryos at E9.5 and E10.5; but a mitotic defect was not apparent at E8.5. The observed decrease in proliferation correlated with decreased expression of cardiac proliferative markers such as n-myc and decrease in proliferative signal pathways in the heart tube.
In conclusion, these data show that, from E9.5 on, CK2α is necessary for proliferation and proliferative signal pathway activation in the heart tube; and that cellular mechanisms other than progenitor incorporation may play a key role in OFT and RV defects.
- © 2012 by American Heart Association, Inc.