Temporal requirement of signaling cascade involving endothelin-1 endothelin receptor type A in branchial arch development
Temporal requirement of signaling cascade involving endothelin-1 endothelin receptor type A in branchial arch development
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DOI：
10.1016/j.mod.2004.05.014
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发表时间：
2004-10-01
影响因子：
2.6
通讯作者：
Kurihara, H
中科院分区：
文献类型：
--
作者：
Fukuhara, S;Kurihara, Y;Kurihara, H
颧弓(BA)系统内的细胞间相互作用是颅面发育所必需的。内皮素-1(ET-1)由鳃上皮和核心间充质产生，作用于表达内皮素A受体(ETAR)的脑神经脊外胚间充质细胞，调节关键基因Dlx6的表达，Dlx6是无远端同源盒基因家族的成员，其下游靶基因DHand是一种基本的螺旋-环-螺旋转录因子。为了研究ET-1和随后的信号级联信号通路在BA发育中的作用，我们研究了它们何时以及如何激活DHand和Dlx6的表达。BQ123阻断Etar在小鼠胚胎培养中的作用表明，ET-1/ETAR信号转导通路在胚胎发育至8.75-E9.0天的下颌弓间充质中对DHand和Dlx6的表达起关键作用，并在胚胎发育到E9.5时变得不可缺少。DHand和Dlx6在E9.5后的表达依赖于上皮的存在，这部分是由成纤维细胞生长因子样信号介导的。这些发现表明，ET-1/ETAR和随后的上皮信号通过维持DHAND和Dlx6的表达而依次参与BA的发生发展。此外，DHand和Dlx6表达结构域的不一致性以及对ET-1和FGF样信号的依赖性的异质性表明，涉及Dlx6和DHand的遗传体系在下颌弓内的不同亚域中受到不同的控制。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
Intercellular interactions within the branchial arch (BA) system is essential for craniofacial development. Endothelin-1 (ET-1), produced by the branchial epithelium and core mesenchyme, acts on cranial neural crest-derived ectomesenchymcal cells expressing endothelin A receptor (ETAR) and regulates expression of crucial genes such as Dlx6, a member of distalless homeobox gene family, and its downstream target dHAND a basic helix-loop-helix transcription factor. To investigate the role of ET-1 and subsequent signaling cascades in BA development, we examined when and how they activate dHAND and Dlx6 expression. ETAR blockade by BQ123 in mouse embryo culture has revealed that ET-1/ETAR signaling is critical for dHAND and Dlx6 expression in the mandibular arch mesenchyme around embryonic day (E)8.75-E9.0 and becomes dispensable by E9.5. dHAND and Dlx6 expression after E9.5 was dependent on the presence of the epithelium, which was partly mediated by FGF-like signals. These findings indicate that ET-1/ETAR and subsequent epithelial signals are sequentially involved in BA development by maintaining dHAND and Dlx6 expression. Furthermore, discordance of dHAND and Dlx6 expression domains and heterogeneity with respect to dependency on ET-1 and FGF-like signals suggest that genetic hierarchy involving Dlx6 and dHAND is differently controlled among subdomains within the mandibular arch. (C) 2004 Elsevier lreland Ltd. All rights reserved.