Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives
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 devel...
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doaj-f75a376d0e9947a199eb00478091e6b82020-11-25T00:31:01ZengElsevierCell Reports2211-12472017-08-012092116213010.1016/j.celrep.2017.08.014Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal DerivativesLaina Freyer0Chih-Wei Hsu1Sonja Nowotschin2Andrea Pauli3Junji Ishida4Keiji Kuba5Akiyoshi Fukamizu6Alexander F. Schier7Pamela A. Hoodless8Mary E. Dickinson9Anna-Katerina Hadjantonakis10Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USADepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USADevelopmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USAThe Research Institute of Molecular Pathology, Vienna BioCenter, 1030 Vienna, AustriaLife Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba 305-8577, JapanDepartment of Biochemistry and Metabolic Science, Akita University, Akita 010-8543, JapanLife Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba 305-8577, JapanDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USATerry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, CanadaDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USADevelopmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USAApela (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.http://www.sciencedirect.com/science/article/pii/S2211124717311063ApelaElabelaEndeToddlerAplnrAPJApelingastrulationcardiovascular developmentmicro-computed tomographymicroCTmacrophagesvascular remodeling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laina Freyer Chih-Wei Hsu Sonja Nowotschin Andrea Pauli Junji Ishida Keiji Kuba Akiyoshi Fukamizu Alexander F. Schier Pamela A. Hoodless Mary E. Dickinson Anna-Katerina Hadjantonakis |
spellingShingle |
Laina Freyer Chih-Wei Hsu Sonja Nowotschin Andrea Pauli Junji Ishida Keiji Kuba Akiyoshi Fukamizu Alexander F. Schier Pamela A. Hoodless Mary E. Dickinson Anna-Katerina Hadjantonakis Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives Cell Reports Apela Elabela Ende Toddler Aplnr APJ Apelin gastrulation cardiovascular development micro-computed tomography microCT macrophages vascular remodeling |
author_facet |
Laina Freyer Chih-Wei Hsu Sonja Nowotschin Andrea Pauli Junji Ishida Keiji Kuba Akiyoshi Fukamizu Alexander F. Schier Pamela A. Hoodless Mary E. Dickinson Anna-Katerina Hadjantonakis |
author_sort |
Laina Freyer |
title |
Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives |
title_short |
Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives |
title_full |
Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives |
title_fullStr |
Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives |
title_full_unstemmed |
Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives |
title_sort |
loss of apela peptide in mice causes low penetrance embryonic lethality and defects in early mesodermal derivatives |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-08-01 |
description |
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. |
topic |
Apela Elabela Ende Toddler Aplnr APJ Apelin gastrulation cardiovascular development micro-computed tomography microCT macrophages vascular remodeling |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717311063 |
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