Deletion of Cdc42 in embryonic cardiomyocytes results in right ventricle hypoplasia

Yang Liu,Rui Wang,Carl W Tong,Shenyuan L Zhang,Binu Tharakan,Jieli Li,Xu Peng,Jian Wang

doi:10.1186/s40169-017-0171-4

Abstract

BackgroundCdc42 is a member of the Rho GTPase family and functions as a molecular switch in regulating cytoskeleton remodeling and cell polarity establishment. Inactivating Cdc42 in cardiomyocytes resulted in embryonic lethality with heart developmental defects, including ventricular septum defects and thin ventricle wall syndrome.FindingsIn this study, we have generated a Cdc42 cardiomyocyte knockout mouse line by crossing Cdc42/flox mice with myosin light chain 2a (MLC2a)-Cre mice. We found that the deletion of Cdc42 in embryonic cardiomyocytes resulted in an underdeveloped right ventricle. Microarray analysis and real-time PCR data analysis displayed that the deletion of Cdc42 decreased dHand expression level. In addition, we found evaginations in the ventricle walls of Cdc42 knockout hearts.ConclusionWe concluded that Cdc42 plays an essential role in right ventricle growth.

Highlights

The mammalian heart is the first functional organ formed during embryogenesis, and it uninterruptedly pumps blood throughout adulthood
To further investigate the role of Cdc42 in heart development, we examined the role of Cdc42 in right ventricle development and found that Cdc42 is required for right ventricle growth
We found that deleting Cdc42 in embryonic cardiomyocytes caused lethality with heart development defects

Summary

Introduction

The mammalian heart is the first functional organ formed during embryogenesis, and it uninterruptedly pumps blood throughout adulthood. Cardiac morphogenesis and maturation require the deployment of multiple cell lineages that are derived from the primary heart field, secondary heart field, and neural crest cells [4,5,6]. The cardiac progenitors that derive from the primary heart field migrate toward the midline of the embryo to fuse and form the primary heart tube. The primary heart tube is elongated by recruiting cells that are generated from the second heart field. Cdc is a member of the Rho GTPase family and functions as a molecular switch in regulating cytoskeleton remodeling and cell polarity establishment. Inactivating Cdc in cardiomyocytes resulted in embryonic lethality with heart developmental defects, including ventricular septum defects and thin ventricle wall syndrome

Methods

Results

Conclusion