Endothelin-1 regulates the dorsoventral branchial arch patterning in mice
Endothelin-1 regulates the dorsoventral branchial arch patterning in mice
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DOI：
10.1016/j.mod.2004.02.002
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发表时间：
2004-04-01
影响因子：
2.6
通讯作者：
Kurihara, H
中科院分区：
文献类型：
--
作者：
Ozeki, H;Kurihara, Y;Kurihara, H
内皮素-1(ET-1)是由鳃弓上皮细胞和核心间充质细胞以及血管内皮细胞分泌的一种由21个氨基酸组成的多肽，它通过神经脊来源的外胚间充质细胞表达的内皮素A型受体(Ednra)参与颅面和心血管的发育。在这里，我们展示了ET-1(-/-)突变小鼠表现出下颌骨到上颌骨的同源类样转变。大多数上颌牙弓来源的成分是复制的，并取代了下颌牙弓来源的结构，导致ET-1(-/-)突变体的上颌和下颌骨的镜像。对于舌骨弓衍生物，与ET-1(-/-)突变体的背侧结构相比，腹侧结构受到严重影响。相应地，在ET-1(-/-)突变体中，Dlx5和Dlx6的表达显著下调，而Dlx2和上颌标记基因Prx2的表达不受影响，或者更确切地说，上调了Dlx2和上颌标记基因Prx2的表达。这些发现表明，ET-1/Ednra信号可能参与了臂弓系统的背腹轴模式，作为区域细胞间相互作用的中介。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
Endothelin-1 (ET-1), a 21-amino acid peptide secreted by the epithelium and core mesenchyme in the branchial arches as well as vascular endothelium, is involved in craniofacial and cardiovascular development through endothelin receptor type-A (EdnrA) expressed in the neural crest-derived ectomesenchyme. Here we show that ET-1(-/-) mutant mice exhibit a homeotic-like transformation of the lower jaw to an upper jaw. Most of the maxillary arch-derived components are duplicated and replaced mandibular arch-derived structures, resulting in a mirror image of the upper and lower jaws in the ET-1(-/-) mutant. As for hyoid arch-derivatives, the ventral structures are severely affected in comparison to the dorsal ones in the ET-1(-/-) mutant. Correspondingly, the expression of Dlx5 and Dlx6, Distalless-related homeobox genes determining the ventral identity of the anterior branchial arches, and of the mandibular marker gene Pitx1 is significantly downregulated in the ET-1(-/-) mutant, whereas the expression of Dlx2 and the maxillary marker gene Prx2 is unaffected or rather upregulated. These findings indicate that the ET-1/EdnrA signaling may contribute to the dorsoventral axis patterning of the branchial arch system as a mediator of the regional intercellular interactions. (C) 2004 Elsevier Ireland Ltd. All rights reserved.