Versican is crucial for the initiation of cardiovascular lumen development in medaka (Oryzias latipes)

Nishant Mittal, Sung Han Yoon, Hirokazu Enomoto, Miyama Hiroshi, Atsushi Shimizu, Atsushi Kawakami, Misato Fujita, Hideto Watanabe, Keiichi Fukuda, Shinji Makino

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16 Citations (Scopus)


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.

Original languageEnglish
Article number9475
JournalScientific reports
Issue number1
Publication statusPublished - 2019 Dec 1

ASJC Scopus subject areas

  • General


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