ZFIN ID: ZDB-PUB-170831-1
Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives
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.
Date: 2017
Source: Cell Reports   20: 2116-2130 (Journal)
Registered Authors: Pauli, Andrea, Schier, Alexander
Keywords: APJ, Apela, Apelin, Aplnr, Elabela, Ende, Toddler, cardiovascular development, gastrulation, macrophages, micro-computed tomography, microCT, vascular remodeling
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Apelin/metabolism
  • Apelin Receptors/metabolism
  • CD11b Antigen/metabolism
  • Carrier Proteins/chemistry
  • Carrier Proteins/metabolism*
  • Embryo Loss/genetics*
  • Embryo Loss/pathology*
  • Embryo, Mammalian/abnormalities
  • Embryo, Mammalian/pathology
  • Embryonic Development
  • Endothelial Cells/metabolism
  • Erythroid Cells/metabolism
  • Gene Expression Regulation, Developmental
  • Mesoderm/embryology*
  • Mesoderm/metabolism*
  • Mice, Knockout
  • Mutation/genetics
  • Myeloid Cells/metabolism
  • Myocardium/pathology
  • Penetrance*
  • Peptides/chemistry
  • Peptides/metabolism*
  • Phenotype
  • Signal Transduction
  • Survival Analysis
  • Up-Regulation/genetics
  • Vascular Remodeling
PubMed: 28854362 Full text @ Cell Rep.
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.