BMP signaling through ACVRI is required for left-right patterning in the early mouse embryo
BMP signaling through ACVRI is required for left-right patterning in the early mouse embryo
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DOI：
10.1016/j.ydbio.2004.08.042
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发表时间：
2004-12-01
影响因子：
2.7
通讯作者：
Mishina, Y
中科院分区：
文献类型：
--
作者：
Kishigami, S;Yoshikawa, SI;Mishina, Y
脊椎动物的特点是背腹和左右不对称。在脊椎动物发育过程中建立左右不对称的过程涉及骨形态发生蛋白（BMP）依赖的信号传导，但这种信号传导途径的分子细节仍然不清楚。本研究测试了BMP I型受体ACVRI在嵌合小鼠胚胎中建立左右不对称性中的作用。使用在Acvr1处具有纯合缺失的小鼠胚胎干（ES）细胞来产生嵌合胚胎。嵌合体胚胎从Acvr1无效胚胎的原肠胚形成缺陷中获救，但表现出异常的心脏循环和胚胎转向。高突变贡献嵌合体表达左侧标记物，例如侧板中胚层（LPM）中双侧的nodal，表明ACVRI信号传导的丧失导致左侧异构。lefty1在嵌合体胚胎的中线中不表达，但中线标记物shh正常表达，表明尽管中线形成，但其屏障功能被废除。高贡献嵌合体也缺乏nodal在淋巴结中的不对称表达。这些数据表明，ACVRI信号负调节左侧的决定因素，如节点和积极调节lefty1。这些功能维持中线，限制左侧标记的表达，并且是小鼠胚胎发生期间左右图案形成所需的。(C)2004年爱思唯尔公司All rights reserved.
Vertebrate organisms are characterized by dorsal-ventral and left-right asymmetry. The process that establishes left-right asymmetry during vertebrate development involves bone morphogenetic protein (BMP)-dependent signaling, but the molecular details of this signaling pathway remain poorly defined. This study tests the role of the BMP type I receptor ACVRI in establishing left-right asymmetry in chimeric mouse embryos. Mouse embryonic stem (ES) cells with a homozygous deletion at Acvr1 were used to generate chimeric embryos. Chimeric embryos were rescued from the gastrulation defect of Acvr1 null embryos but exhibited abnormal heart looping and embryonic turning. High mutant contribution chimeras expressed left-side markers such as nodal bilaterally in the lateral plate mesoderm (LPM), indicating that loss of ACVRI signaling leads to left isomerism. Expression of lefty1 was absent in the midline of chimeric embryos, but shh, a midline marker, was expressed normally, suggesting that, despite formation of midline, its barrier function was abolished. High-contribution chimeras also lacked asymmetric expression of nodal in the node. These data suggest that ACVRI signaling negatively regulates left-side determinants such as nodal and positively regulates lefty1. These functions maintain the midline, restrict expression of left-side markers, and are required for left-right pattern formation during embryogenesis in the mouse. (C) 2004 Elsevier Inc. All rights reserved.