Loss of Apela peptide in mice causes low penetrance embryonic lethality and defects in early mesodermal derivatives Journal Article

   

Authors:	Freyer, L.; Hsu, C. W.; Nowotschin, S.; Pauli, A.; Ishida, J.; Kuba, K.; Fukamizu, A.; Schier, A. F.; Hoodless, P. A.; Dickinson, M. E.; Hadjantonakis, A. K.
Article Title:	Loss of Apela peptide in mice causes low penetrance embryonic lethality and defects in early mesodermal derivatives
Abstract:	Apela (also known as Elabela, Ende, and Toddler) is a small signaling peptide that activates the G-protein-coupled receptor Aplnr to stimulate cell migration during zebrafish gastrulation. Here, using CRISPR/Cas9 to generate a null, reporter-expressing allele, we study the role of Apela in the developing mouse embryo. We found that loss of Apela results in low-penetrance cardiovascular defects that manifest after the onset of circulation. Three-dimensional micro-computed tomography revealed a higher penetrance of vascular remodeling defects, from which some mutants recover, and identified extraembryonic anomalies as the earliest morphological distinction in Apela mutant embryos. Transcriptomics at late gastrulation identified aberrant upregulation of erythroid and myeloid markers in mutant embryos prior to the appearance of physical malformations. Double-mutant analyses showed that loss of Apela signaling impacts early Aplnr-expressing mesodermal populations independently of the alternative ligand Apelin, leading to lethal cardiac defects in some Apela null embryos. © 2017 The Author(s)
Keywords:	micro-computed tomography; macrophages; gastrulation; vascular remodeling; cardiovascular development; apela; apelin; apj; aplnr; elabela; ende; microct; toddler
Journal Title:	Cell Reports
Volume:	20
Issue:	9
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2017-08-29
Start Page:	2116
End Page:	2130
Language:	English
DOI:	10.1016/j.celrep.2017.08.014
PROVIDER:	scopus
PMCID:	PMC5580402
PUBMED:	28854362
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85028422822&doi=10.1016%2fj.celrep.2017.08.014&partnerID=40&md5=b4216c6e1a39d780b2b233116fde66eb
Notes:	Article -- Export Date: 2 October 2017 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/115529