Abstract:
Apelin receptor (APJ) provides cellular instructions for cardiovascular development in mice.
During embryonic mouse heart development, APJ is expressed by a small subset of cardiac
progenitors found in the second heart field (SHF) region. We show that APJ+ cells contribute to
the cells of outflow tract (OFT), which eventually give rise to aorta and pulmonary trunk upon its
morphogenesis. The role of APJ in SHF domain is unclear. The main objective of this research is
to identify the exact role of APJ in outflow tract development by analyzing its function early in
cardiac progenitors in the SHF and later in the events of OFT morphogenesis. We hypothesize
that APJ stimulate SHF progenitor cell growth and contribute to the morphogenesis of aorta and
pulmonary trunk. To address this hypothesis, we studied the effect of SHF progenitor cell
specific Apj gene deletion on the proliferation and survival of OFT progenitors in the SHF
domain and its impact on the morphogenesis of OFT in the developing heart. Our data suggested
that the deletion of Apj gene reduced the proliferation of SHF progenitors, while there was no
significant impact of Apj deletion on survival of the SHF progenitors. Morphological analysis by
whole mount immunostaining of intact whole heart revealed double outlet ventricle and
misalignment of aorta and pulmonary trunk. Moreover, the Apj deletion led to OFT related
phenotypes. Our findings provide a novel role for APJ in the regulation of SHF cardiac progenitors and their contributions to aorta and pulmonary trunk formation.
