RRC ID 59223
Author Mittal N, Yoon SH, Enomoto H, Hiroshi M, Shimizu A, Kawakami A, Fujita M, Watanabe H, Fukuda K, Makino S.
Title Versican is crucial for the initiation of cardiovascular lumen development in medaka (Oryzias latipes).
Journal Sci Rep
Abstract Versican is an evolutionary conserved extracellular matrix proteoglycan, and versican expression loss in mice results in embryonic lethality owing to cardiovascular defects. However, the in utero development of mammals limits our understanding of the precise role of versican during cardiovascular development. Therefore, the use of evolutionarily distant species that develop ex utero is more suitable for studying the mechanistic basis of versican activity. We performed ENU mutagenesis screening to identify medaka mutants with defects in embryonic cardiovascular development. In this study, we described a recessive point mutation in the versican 3'UTR resulting in reduced versican protein expression. The fully penetrant homozygous mutant showed termination of cardiac development at the linear heart tube stage and exhibited absence of cardiac looping, a constricted outflow tract, and no cardiac jelly. Additionally, progenitor cells did not migrate from the secondary source towards the arterial pole of the linear heart tube, resulting in a constricted outflow tract. Furthermore, mutants lacked blood flow and vascular lumen despite continuous peristaltic heartbeats. These results enhance our understanding of the mechanistic basis of versican in cardiac development, and this mutant represents a novel genetic model to investigate the mechanisms of vascular tubulogenesis.
Volume 9(1)
Pages 9475
Published 2019-7-1
DOI 10.1038/s41598-019-45851-3
PII 10.1038/s41598-019-45851-3
PMID 31263118
PMC PMC6603046
MeSH 3' Untranslated Regions Animals Fish Proteins / genetics Fish Proteins / metabolism* Heart / embryology* Organogenesis* Oryzias / embryology* Oryzias / genetics Point Mutation Versicans / genetics Versicans / metabolism*
IF 3.998
Times Cited 0
Medaka Hatching enzyme fli::GFP (TG1206) HNI-II (IB176) Qurt (MT828) AD-1/GFP (TG126) ki206, big heart tube (MT328) (linear heart tube (lht))