Pitx2c attenuation results in cardiac defects and abnormalities of intestinal orientation in developing Xenopus laevis
Pitx2c attenuation results in cardiac defects and abnormalities of intestinal orientation in developing Xenopus laevis
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DOI：
10.1016/s0012-1606(03)00389-0
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发表时间：
2003-10-15
影响因子：
2.7
通讯作者：
Weeks, DL
中科院分区：
文献类型：
--
作者：
Dagle, JM;Sabel, JL;Weeks, DL
早期胚胎学事件的实验操作，导致同源异型盒转录因子pitx 2的错误表达，与随后的缺陷，在一些脊椎动物系统的偏侧性。为了阐明一个pitx2亚型，pitx2c，在确定两栖动物胚胎的左右轴的作用，我们研究了非洲爪蟾胚胎的心脏和肠道形态衰减pitx2c的mRNA水平后，使用化学修饰的反义寡核苷酸。我们证明，在这些胚胎中的pitx2c mRNA的部分耗尽的结果在心脏形态和肠卷曲的改变。观察到的最常见的心脏异常是流出道的肌层迁移失败，而观察到的最常见的肠偏侧性表型是卷曲方向的完全逆转，每种都存在于注射pitx2c反义寡核苷酸的23%的胚胎中。心脏或肠道的异常进一步导致另一个的畸形。此外，在pitx2c mRNA衰减后观察到许多其他心脏异常，包括房间隔异常、细胞外基质限制、相对房室腔定位和心室发育限制。许多这些发现与心脏缺陷先前报告的pitx2 null和hypomorphic小鼠，但现在可以具体分配到衰减的pitx2c异构体在非洲爪蟾。(C)2003年爱思唯尔公司All rights reserved.
The experimental manipulation of early embryologic events, resulting in the misexpression of the homeobox transcription factor pitx2, is associated with subsequent defects of laterality in a number of vertebrate systems. To clarify the role of one pitx2 isoform, pitx2c, in determining the left-right axis of amphibian embryos, we examined the heart and gut morphology of Xenopus laevis embryos after attenuating pitx2c mRNA levels using chemically modified antisense oligonucleotides. We demonstrate that the partial depletion of pitx2c mRNA in these embryos results in alteration of both cardiac morphology and intestinal coiling. The most common cardiac abnormality seen was a failure of rightward migration of the outflow tract, while the most common intestinal laterality phenotype seen was a full reversal in the direction of coiling, each present in 23% of embryos injected with the pitx2c antisense oligonucleotide. An abnormality in either the heart or gut further predisposed to a malformation in the other. In addition, a number of other cardiac anomalies were observed after pitx2c mRNA attenuation, including abnormalities of atrial septation, extracellular matrix restriction, relative atrial-ventricular chamber positioning, and restriction of ventricular development. Many of these findings correlate with cardiac defects previously reported in pitx2 null and hypomorphic mice, but can now be assigned specifically to attenuation of the pitx2c isoform in Xenopus. (C) 2003 Elsevier Inc. All rights reserved.