title: Xapelin and Xmsr are required for cardiovascular development in Xenopus laevis.
abstract: The cardiovascular development is the elaborate process, and despite the extensive studies, the mechanisms underlying endothelial, hematopoietic, and cardiac developments, as well as the interrelation between these processes, are not fully understood. In this study, we demonstrated that Xenopus apelin and Xmsr play pivotal roles in cardiovascular development. Apelin is a recently identified ligand for an orphan G-protein-coupled receptor APJ and is involved in fluid homeostasis in mammals. Xenopus preproapelin (Xpreproapelin) was isolated and its mRNA localized to the region around the presumptive blood vessels, which are overlapping or adjacent to those expressing Xmsr, the Xenopus homologue of APJ. Overexpression of Xpreproapelin disorganized the expression of the endothelial precursor cell marker XlFli and the hematopoietic precursor cell marker SCL at the neurula, whereas embryos injected with morpholino antisense oligonucleotides for Xapelin and Xmsr displayed attenuated expression of Tie2, alpha-globin, XPOX2, and cTnI, markers of endothelium, erythrocytes, myeloid cells, and cardiomyocytes, respectively. XlFli morpholino had similar effects to Xapelin and Xmsr morpholinos on cardiac differentiation, suggesting an unexpected potential relationship between the endothelium and cardiac differentiation. Forced expression of constitutive active G alpha i rescued the phenotypes of Xmsr morpholino-injected embryos, indicating that the i/o type of G protein alpha subunit acts downstream of Xmsr.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inui
authors.forename: Akimasa
authors.initials: A
authors.lastname: Fukui
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ito
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002319:Cardiovascular System / Q000196:embryology* / Q000378:metabolism; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian; D042783:Endothelial Cells / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009024:Morphogenesis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: C513482:APLN protein, Xenopus; C105530:APLNR protein, Xenopus; D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D029867:Xenopus Proteins