Hedgehog/Patched-associated rhabdomyosarcoma formation from delta1-expressing mesodermal cells
Hedgehog/Patched-associated rhabdomyosarcoma formation from delta1-expressing mesodermal cells
复制标题
表达 delta1 的中胚层细胞形成 Hedgehog/斑片相关横纹肌肉瘤
作者：
Nitzki F;Cuvelier N;Dräger J;Schneider A;Braun T;Hahn H
横纹肌肉瘤(RMS)是儿科最常见的软组织肉瘤。在儿童中，RMS的两个主要亚型是肺泡型和胚胎型。Hedgehog/Patched1(HH/PTCH)信号异常是胚胎期RMS的标志。我们证明，在表达Delta1的中胚层细胞中携带Ptch突变的小鼠发展为胚胎样RMS的速度与在胚系或表达短小胚层的中胚层中携带Ptch突变的小鼠相似。当Ptch在Myf5或Pax3表达的细胞中发生突变时，肿瘤发生率显著降低。Mygenin/MEF2C表达的细胞无RMS发生。这表明HH/PTCH相关的RMS来源于Delta1阳性、Myf5阴性、Mygenin阴性和Pax3阴性的中胚层祖细胞，这些祖细胞可以进行肌源性分化，但缺乏稳定的谱系承诺。更多的初步遗传学数据和关于中胚层前体细胞的数据进一步暗示在RMS启动过程中HH/PTCH和Delta/Notch信号活性的相互作用。相反，Wnt信号被认为抑制RMS的形成，因为RMS的多重性在Wnt抑制剂Wif1失活后降低。最后，我们的结果有力地表明，肿瘤启动事件决定了RMS起源的谱系。
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. In children, the 2 major RMS subtypes are alveolar and embryonal RMS. Aberrant Hedgehog/Patched1 (Hh/Ptch) signaling is a hallmark of embryonal RMS. We demonstrate that mice carrying a Ptch mutation in mesodermal Delta1-expressing cells develop embryonal-like RMS at a similar rate as mice harboring a Ptch mutation in the germline or the brachury-expressing mesoderm. The tumor incidence decreases dramatically when Ptch is mutated in Myf5-or Pax3-expressing cells. No RMS develop from Myogenin/Mef2c-expressing cells. This suggests that Hh/Ptch-associated RMS are derived from Delta1-positive, Myf5-negative, Myogenin-negative and Pax3-negative mesodermal progenitors that can undergo myogenic differentiation but lack stable lineage commitment. Additional preliminary genetic data and data on mesodermal progenitors further imply an interplay of Hh/Ptch and Delta/Notch signaling activity during RMS initiation. In contrast, Wnt signals supposedly suppress RMS formation because RMS multiplicity decreases after inactivation of the Wnt-inhibitor Wif1. Finally, our results strongly suggest that the tumor-initiating event determines the lineage of RMS origin.
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内侧皮肌节的形成需要来自背侧神经管的 Wnt 信号传导。
影响因子：
4.6
作者：
M. Ikeya;S. Takada
通讯作者：
S. Takada
影响因子：
10.5
作者：
Langenau, David M.;Keefe, Matthew D.;Zon, Leonard I.
通讯作者：
Zon, Leonard I.
影响因子：
50.3
作者：
Hatley ME;Tang W;Garcia MR;Finkelstein D;Millay DP;Liu N;Graff J;Galindo RL;Olson EN
通讯作者：
Olson EN
DOI：
--
发表时间：
2013
期刊：
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie
影响因子：
--
作者：
S. Diaconescu;M. Burlea;I. Miron;S. Aprodu;D. Mihǎilǎ;C. Olaru;Lucian Miron
通讯作者：
Lucian Miron
影响因子：
10.5
作者：
Greco, TL;Takada, S;Camper, SA
通讯作者：
Camper, SA