Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Molecular Genetics

Background:

• NOTCH signaling in the endocardium is vital for vertebrate heart development, including trabeculation and valve formation.
• The specific role of NOTCH signaling within the myocardium during cardiac development remains largely uncharacterized.

Purpose of the Study:

• To investigate the physiological role of NOTCH signaling in myocardial development.
• To determine the consequences of disrupting NOTCH-RBPJ signaling specifically in cardiomyocytes.

Main Methods:

• Utilized mouse genetics to specifically delete the NOTCH effector RBPJ in early cardiomyocyte progenitors using Tnnt2-Cre.
• Examined cardiac development and function in homozygous mutant mice lacking RBPJ in the myocardium.
• Also performed deletion of RBPJ in both myocardial and endocardial progenitors using Nkx2.5-Cre for comparison.

Main Results:

• Myocardial-specific deletion of RBPJ (or Notch1) did not affect cardiac development markers or adult heart function in mice.
• Homozygous mutant mice with myocardial RBPJ deletion developed normally to term.
• Deletion of RBPJ in both myocardial and endocardial progenitors led to severe cardiac defects, including VSD, DORV, and BAV, confirming the critical role of endocardial NOTCH signaling.

Conclusions:

• NOTCH-RBPJ signaling is dispensable for myocardial development and adult cardiac function.
• Endocardial NOTCH signaling, however, is essential for proper cardiac valve morphogenesis and septation.
• These findings highlight the distinct roles of NOTCH signaling in different cardiac cell lineages.