RRC ID 20971
Author Miyanishi H, Okubo K, Nobata S, Takei Y.
Title Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss-of-function studies.
Journal Endocrinology
Abstract Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP), and their receptor, guanylyl cyclase (GC)-A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions. In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses. Medaka has two ligands, BNP and C-type NP3 (CNP3) (but not ANP), that have greater affinity for the two O. latipes GC-A receptors (OLGC), OLGC7 and OLGC2, respectively. CNP3 is the ancestral molecule of cardiac NPs. Initially, we examined developmental expression of cardiac NP/receptor combinations, BNP/OLGC7 and CNP3/OLGC2, using quantitative real-time PCR and in situ hybridization. BNP and CNP3 mRNA increased at stages 25 (onset of ventricular formation) and 22 (appearance of heart anlage), respectively, whereas both receptor mRNAs increased at as early as stage 12. BNP/OLGC7 transcripts were found in arterial/ventricular tissues and CNP3/OLGC2 transcripts in venous/atrial tissues by in situ hybridization. Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine/autocrine fashion. Double knockdown of BNP/OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation. CNP3 knockdown induced hypertrophy of atria and activated the renin-angiotensin system. Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates. The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates.
Volume 154(1)
Pages 410-20
Published 2013-1-1
DOI 10.1210/en.2012-1730
PII en.2012-1730
PMID 23183183
MeSH Animals Atrial Natriuretic Factor / genetics Atrial Natriuretic Factor / metabolism Embryo, Nonmammalian / metabolism* In Situ Hybridization Natriuretic Peptide, Brain / genetics Natriuretic Peptide, Brain / metabolism Natriuretic Peptides / genetics Natriuretic Peptides / metabolism* Oryzias / genetics Oryzias / metabolism* Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction
IF 3.934
Times Cited 7
Medaka d-rR/TOKYO (MT837) Hatching enzyme