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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number9475
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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Versicans
Oryzias
Blood Vessels
Genetic Models
Proteoglycans
Point Mutation
Mutagenesis
Embryonic Development
Extracellular Matrix
Mammals
Stem Cells

ASJC Scopus subject areas

  • General

Cite this

Versican is crucial for the initiation of cardiovascular lumen development in medaka (Oryzias latipes). / Mittal, Nishant; Yoon, Sung Han; Enomoto, Hirokazu; Hiroshi, Miyama; Shimizu, Atsushi; Kawakami, Atsushi; Fujita, Misato; Watanabe, Hideto; Fukuda, Keiichi; Makino, Shinji.

In: Scientific reports, Vol. 9, No. 1, 9475, 01.12.2019.

Research output: Contribution to journalArticle

Mittal, N, Yoon, SH, Enomoto, H, Hiroshi, M, Shimizu, A, Kawakami, A, Fujita, M, Watanabe, H, Fukuda, K & Makino, S 2019, 'Versican is crucial for the initiation of cardiovascular lumen development in medaka (Oryzias latipes)', Scientific reports, vol. 9, no. 1, 9475. https://doi.org/10.1038/s41598-019-45851-3
Mittal, Nishant ; Yoon, Sung Han ; Enomoto, Hirokazu ; Hiroshi, Miyama ; Shimizu, Atsushi ; Kawakami, Atsushi ; Fujita, Misato ; Watanabe, Hideto ; Fukuda, Keiichi ; Makino, Shinji. / Versican is crucial for the initiation of cardiovascular lumen development in medaka (Oryzias latipes). In: Scientific reports. 2019 ; Vol. 9, No. 1.
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