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异质毒性基因GALNT11糖化了Notch,以调节乳毛类型和横向性

Marko T Boskovski¹, Shiaulou Yuan², Nis Borbye Pedersen³

¹1] Program in Vertebrate Developmental Biology, Department of Pediatrics and Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [2] [3] Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.

|November 15, 2013

概括

N-乙-氨酸胺类型O-糖化酶GALNT11对于通过平衡移动和不移动的眼来确定身体左右模式 (侧面性) 是至关重要的. 这一发现揭示了一种新的异质毒性机制,异质毒性是一种与先天性心脏病相关的疾病.

科学领域:

发育生物学发展生物学
细胞生物学细胞生物学
遗传学是一个遗传学.

背景情况:

异质性是一种与先天性心脏缺陷相关的左右身体模式障碍.
人类异质毒性背后的机制以及胚胎左右组织者的乳头类型的规范性是鲜为人知的.
移动的毛产生向左流,被不移动的毛检测到,以启动横向的不对称信号.

研究的目的:

调查GALNT11在确定胚胎左右组织者的乳毛类型规范中的作用.
阐明GALNT11影响横向性决定的分子机制.
为了确定涉及到人类异质毒素的新途径.

主要方法:

使用Xenopus tropicalis作为一个模型生物.
研究了galnt11和Notch信号在毛发育中的功能.
在人体NOTCH1的体外糖化试验中使用.
开发了对胚胎毛的定量实时成像技术.
枯竭的galnt11或notch1和过度表达的Notch,以观察对眼比率和横向性的影响.

主要成果:

证明GALNT11对于在左右组织者中指定运动性与不运动性乳毛至关重要.
表明GALNT11激活了Notch信号,可能是通过NOTCH1.1.的直接O-糖化激活NOTCH1.
发现Galnt11介导的Notch信号调节了运动和不运动的空间分布和比例.
galnt11或notch1的耗尽导致了横向性缺陷,其特点是多余的移动毛.
突出的过度表达导致移动性乳毛减少,模仿乳毛病.

结论:

在左右组织器中,GALNT11在建立运动和不运动之间的正确平衡方面发挥着至关重要的作用.
这种平衡,由Galnt11依赖的Notch信号传递介导,对于确定左右身体横向性至关重要.
这种途径的失调代表了一种新的机制,有助于人类异质毒性和相关的先天性心脏病.

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