Smad signaling in the neural crest regulates cardiac outflow tract remodeling through cell autonomous and non-cell autonomous effects
Smad signaling in the neural crest regulates cardiac outflow tract remodeling through cell autonomous and non-cell autonomous effects
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DOI：
10.1016/j.ydbio.2007.08.044
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发表时间：
2007-11-01
影响因子：
2.7
通讯作者：
Chen, Feng
中科院分区：
文献类型：
--
作者：
Jia, Qunshan;McDill, Bradley W.;Chen, Feng
神经嵴细胞（NCC）对于心脏流出道（OFT）的发育是不可或缺的。在这里，我们发现 NCC 中缺乏 Smad4 的小鼠具有持续性动脉干 (PTA)、严重的 OFT 垫发育不全、OFT 伸长缺陷和 OFT 错位。缺乏 Smad4 的心脏 NCC 细胞凋亡增加，显然是由于 Msx1/2 表达减少。这有助于减少 OFT 中的 NCC。出乎意料的是，突变体在第二心区 (SHE) 内的内脏中胚层中具有表达 MF20 的心肌细胞。这可能是由于分化异常的 SHE 细胞向 OFT 的募集缺陷造成的。突变型 OFT、SHE 和 NCC 中 Bmp4、Sema3C 和 PlexinA2 信号的改变会破坏不同细胞群之间的通讯。这种破坏会进一步影响 NCC 招募到 OFT 间充质中，导致严重的 OFT 垫发育不全和 OFT 分隔失败。此外，这些NCC大大降低了Ids和MT1-MMP的水平，影响了OFT的定位和重塑。因此，心脏 NCC 中的 Smad 信号传导对其生存具有细胞自主效应，对协调多个细胞谱系在 OFT 定位和重塑中的运动具有非细胞自主效应。 (C) 2007 Elsevier Inc. 保留所有权利。
Neural crest cells (NCCs) are indispensable for the development of the cardiac outflow tract (OFT). Here, we show that mice lacking Smad4 in NCCs have persistent truncus arteriosus (PTA), severe OFT cushion hypoplasia, defective OFT elongation, and mispositioning of the OFT. Cardiac NCCs lacking Smad4 have increased apoptosis, apparently due to decreased Msx1/2 expression. This contributes to the reduction of NCCs in the OFT. Unexpectedly, mutants have MF20-expressing cardiomyocytes in the splanchnic mesoderm within the second heart field (SHE). This may result from abnormal differentiation or defective recruitment of differentiating SHE cells into OFT. Alterations in Bmp4, Sema3C, and PlexinA2 signals in the mutant OFT, SHE, and NCCs, disrupt the communications among different cell populations. Such disruptions can further affect the recruitment of NCCs into the OFT mesenchyme, causing severe OFT cushion hypoplasia and OFT septation failure. Furthermore, these NCCs have drastically reduced levels of Ids and MT1-MMP, affecting the positioning and remodeling of the OFT. Thus, Smad-signaling in cardiac NCCs has cell autonomous effects on their survival and non-cell autonomous effects on coordinating the movement of multiple cell lineages in the positioning and the remodeling of the OFT. (C) 2007 Elsevier Inc. All rights reserved.