| RRC ID |
71499
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| 著者 |
Daisuke Kobayashi, Kazuhiko Matsuo, Tetsuaki Kimura, Satoshi Ansai, Hayato Yokoi, Shigeo Takashima, Tadao Kitagawa, Takahiro Kage, Takanori Narita, Tomoko Jindo, Masato Kinoshita, Kiyoshi Naruse, Yoshiro Nakajima, Masaki Shigeta, Shinichiro Sakaki, Satoshi Inoue, Rie Saba, Kei Yamada, Takahiko Yokoyama, Yuji Ishikawa, Kazuo Araki, Yumiko Saga, Hiroyuki Takeda, Kenta Yashiro
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| タイトル |
Myosin phosphatase target subunit 1 governs integrity of the embryonic gut epithelium to circumvent atresia development in medaka, Oryzias latipes
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| Abstract |
BackgroundIntestinal atresia (IA) is a congenital gut obstruction caused by the absence of gut opening. Genetic factors are assumed to be critical for the development of IA, in addition to accidental vascular insufficiency or mechanical strangulation. However, the molecular mechanism underlying IA remains poorly understood.ResultsIn this study, to better understand such a mechanism, we isolated a mutant of Oryzias latipes (the Japanese rice fish known as medaka) generated by N-ethyl-N-nitrosourea mutagenesis, in which IA develops during embryogenesis. Positional cloning identified a nonsense mutation in the myosin phosphatase target subunit 1 (mypt1) gene. Consistent with known Mypt1 function, the active form of myosin regulatory light chain (MRLC), which is essential for actomyosin contraction, and F-actin were ectopically accumulated in the intestinal epithelium of mutant embryos, whereas cell motility, proliferation and cell death were not substantially affected. Corresponding to the accumulation site of F-actin/active MRLC, the intestinal epithelium architecture was disordered. Importantly, blebbistatin, a non-muscle myosin inhibitor, attenuated the development of IA in the mutant.ConclusionsCytoskeletal contraction governed by mypt1 regulates the integrity of the embryonic intestinal epithelium. This study provides new insight into our understanding of the mechanism of IA development in humans.Bullet PointsMedaka mypt1 mutants display intestinal atresia.The level of phosphorylated myosin regulatory light chain was higher in mypt1 mutant embryos than in wild-type embryos.The levels of F-actin appeared elevated in the intestinal epithelium of mypt1 mutants.Blebbistatin, an inhibitor of non-muscle myosin II, rescued intestinal atresia in mypt1 mutant embryos.
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| DOI |
10.1101/2021.12.10.472183
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| リソース情報 |
| メダカ |
孵化酵素
d-rR/TOKYO (MT837)
G1-4 (MT147) |
