BACKGROUND: The small GTPase @entity5844 regulates diverse cellular functions, including both apicobasal and planar cell polarity pathways; however, its role in cardiac outflow tract (OFT) development remains unknown. In the present study, we aimed to examine the role of @entity5844 in the anterior second heart field ( @entity70021 ) splanchnic mesoderm and subsequent OFT development during heart morphogenesis. METHODS AND RESULTS: Using the Cre/loxP system, @entity19 with an anterior @entity70021 -specific deletion of @entity5844 ( @entity70021 ) were generated. Embryos were collected at various developmental time points for immunostaining and histological analysis. Intrauterine echocardiography was also performed to assess aortic valve blood flow in embryos at embryonic day 18.5. The @entity70021 splanchnic mesoderm exhibited disruptions in @entity70021 progenitor cellular organization and proliferation. Consequently, this led to a spectrum of OFT defects along with @entity886 in @entity70021 embryos. Mechanistically, it was found that the ability of the @entity5844 myocardial cells to migrate into the proximal OFT cushion was severely reduced. In addition, expression of the neural crest chemoattractant semaphorin 3c was decreased. Lineage tracing showed that anterior @entity70021 contribution to the OFT myocardium and aortic valves was deficient in @entity70021 hearts. Furthermore, functional analysis with intrauterine echocardiography at embryonic day 18.5 showed @entity337 in @entity70021 hearts, which was not seen in control hearts. CONCLUSIONS: Disruptions of @entity5844 signaling in the anterior @entity70021 results in aberrant progenitor cellular organization and defects in OFT development. Our data show @entity5844 signaling to be a critical regulator of cardiac OFT formation during embryonic heart development.

XXXX Signaling Is Required for Anterior Second Heart Field Cellular Organization and Cardiac Outflow Tract Development.

@entity19 :: ('10090', 'Species') :: ['mice'] @entity886 :: ('MESH:C563178', 'Disease') :: ['aortic valve defects'] @entity5844 :: ('19353(Tax:10090)', 'Gene') :: ['Rac1(SHF) OFT', 'Rac1'] @entity337 :: ('MESH:D001022', 'Disease') :: ['aortic valve regurgitation'] @entity70021 :: ('435684(Tax:10090)', 'Gene') :: ['Rac1(SHF)', 'SHF']
@entity5844 :: (19353(Tax:10090),Gene) :: ['Rac1']
