RFX2 is essential in the ciliated organ of asymmetry and an RFX2 transgene identifies a population of ciliated cells sufficient for fluid flow.
RFX2 is essential in the ciliated organ of asymmetry and an RFX2 transgene identifies a population of ciliated cells sufficient for fluid flow.
复制标题
DOI：
10.1016/j.ydbio.2011.12.030
复制
发表时间：
2012-03-01
影响因子：
2.7
通讯作者：
Brueckner M
中科院分区：
文献类型：
--
作者：
Bisgrove BW;Makova S;Yost HJ;Brueckner M
运动纤毛在进化上保守的纤毛不对称器官（COA）中产生不对称的流体流动，并在脊椎动物胚胎中建立左右（LR）轴中发挥重要作用。编码有助于纤毛结构和功能的蛋白质的一大组基因的转录控制仍然知之甚少。在这项研究中，我们发现有翼螺旋转录因子Rfx 2在小鼠和斑马鱼胚胎的运动纤毛中表达。在整个胚胎中或特别是在斑马鱼COA（Kupffer囊泡，KV）的细胞中Rfx 2功能的吗啉代敲低导致KV纤毛长度减少和LR不对称性的扰动。LR模式缺陷包括早期不对称Nodal信号通路基因southpaw、lefty 1和lefty 2的随机化以及随后心脏和肠道器官原基的逆转。Rfx 2也是斑马鱼前肾管纤毛发生所需的。我们进一步表明，通过恢复左-右动力蛋白（LRD）的表达和运动性，特别是在小鼠COA（后脊索，PNC）的纤毛细胞的子集，我们可以恢复流体流动，不对称表达的Pitx 2和部分挽救原位缺陷。
Motile cilia create asymmetric fluid flow in the evolutionarily conserved ciliated organ of asymmetry (COA) and play a fundamental role in establishing the left-right (LR) axis in vertebrate embryos. The transcriptional control of the large group of genes that encode proteins that contribute to ciliary structure and function remains poorly understood. In this study we find that the winged helix transcription factor Rfx2 is expressed in motile cilia in mouse and zebrafish embryos. Morpholino knockdown of Rfx2 function in the whole embryo or specifically in cells of the zebrafish COA (Kupffer’s Vesicle, KV) leads to reduced KV cilia length and perturbations in LR asymmetry. LR patterning defects include randomization of the early asymmetric Nodal signaling pathway genes southpaw, lefty1 and lefty2 and subsequent reversals in the organ primordia of the heart and gut. Rfx2 is also required for ciliogenesis in zebrafish pronephric duct. We further show that by restoring Left-Right dynein (LRD) expression and motility specifically in a subset of ciliated cells of the mouse COA (posterior notochord, PNC), we can restore fluid flow, asymmetric expression of Pitx2 and partially rescue situs defects.
登录
查看更多内容
影响因子：
64.8
作者：
Essner, JJ;Vogan, KJ;Brueckner, M
通讯作者：
Brueckner, M
影响因子：
9.2
作者：
Amack, JD;Yost, HJ
通讯作者：
Yost, HJ
影响因子：
2.9
作者：
Blum, Martin;Andre, Philipp;Viebahn, Christoph
通讯作者：
Viebahn, Christoph
IFT驱动素的功能调节扩展了秀丽隐杆线虫中纤毛神经元的感觉曲目。
影响因子：
7.8
作者：
Evans, JE;Snow, JJ;Gunnarson, AL;Ou, GS;Stahlberg, H;McDonald, KL;Scholey, JM
通讯作者：
Scholey, JM
影响因子：
2.7
作者：
Chung MI;Peyrot SM;LeBoeuf S;Park TJ;McGary KL;Marcotte EM;Wallingford JB
通讯作者：
Wallingford JB