Shh/Ptch and EGF/ErbB cooperatively regulate branching morphogenesis of fetal mouse submandibular glands
Shh/Ptch and EGF/ErbB cooperatively regulate branching morphogenesis of fetal mouse submandibular glands
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DOI：
10.1016/j.ydbio.2016.02.018
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发表时间：
2016-04-15
影响因子：
2.7
通讯作者：
Kashimata, Masanori
中科院分区：
文献类型：
--
作者：
Mizukoshi, Kenji;Koyama, Noriko;Kashimata, Masanori
刺猬家族包括Sonic hedgehog（Shh）、Desert hedgehog和Indian hedgehog，它们被认为是在许多器官如舌、胰腺、肾脏、软骨、牙齿和唾液腺（SMG）的发育过程中发挥许多重要作用的形态发生素。在Shh基因敲除小鼠中，在胚胎第14天（E14）后观察到唾液腺的异常发育。在培养的E14 SMG中，Shh还诱导腺泡样结构中的小叶形成和管腔形成。在这项研究中，我们研究了Shh和表皮生长因子（EGF）/ErbB信号在发育中的胎鼠SMG之间的关系。培养的E13 SMG的管理Shh刺激分支形态发生（BrM）和诱导合成的EGF配体和受体的ErbB家族的mRNA。Shh还刺激ErbB信号系统如ERK 1/2的激活。ErbB受体特异性抑制剂AG 1478可完全抑制BrM和EGF/ErbB/ERK 1/2级联反应。Shh可特异性诱导E13 SMG间充质中Egf mRNA和上皮中Erbb 1、Erbb 2和Erbb 3 mRNA的表达。这些结果表明Shh至少部分地通过激活EGF/ErbB/ERK 1/2信号系统刺激胎鼠SMG的BrM。(C)2016 Elsevier Inc. All rights reserved.
The hedgehog family includes Sonic hedgehog (Shh), Desert hedgehog, and Indian hedgehog, which are well known as a morphogens that play many important roles during development of numerous organs such as the tongue, pancreas, kidney, cartilage, teeth and salivary glands (SMG). In Shh null mice, abnormal development of the salivary gland is seen after embryonic day 14 (E14). Shh also induced lobule formation and lumen formation in acini-like structures in cultured E14 SMG. In this study, we investigated the relationship between Shh and epidermal growth factor (EGF)/ErbB signaling in developing fetal mouse SMG. Administration of Shh to cultured E13 SMG stimulated branching morphogenesis (BrM) and induced synthesis of mRNAs for EGF ligands and receptors of the ErbB family. Shh also stimulated activation of ErbB signaling system such as ERK1/2. AG1478, a specific inhibitor of ErbB receptors, completely suppressed BrM and activation of EGF/ErbB/ERK1/2 cascade in E13 SMGs cultured with Shh. The expressions of mRNA for Egf in mesenchyme and mRNA for Erbb1, Erbb2 and Erbb3 in epithelium of E13 SMG were specifically induced by administration of Shh. These results show that Shh stimulates BrM of fetal mouse SMG, at least in part, through activation of the EGF/ErbB/ERK1/2 signaling system. (C) 2016 Elsevier Inc. All rights reserved.