Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development.
Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development.
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DOI：
10.1038/s41598-017-06964-9
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发表时间：
2017-07-28
影响因子：
4.6
通讯作者：
Yamagishi H
中科院分区：
文献类型：
--
作者：
Kodo K;Shibata S;Miyagawa-Tomita S;Ong SG;Takahashi H;Kume T;Okano H;Matsuoka R;Yamagishi H
心脏神经嵴细胞（cNCCs）和第二心区（SHF）在脊椎动物心脏流出道（OFT）的发育中起着关键作用，以建立完全分离的肺循环和体循环。一种神经血管导向因子，信号素3c（Sema3c），是流出道发育所必需的，然而，它对cNCCs和SHF之间相互作用的调节仍有待确定。在此，我们表明Sema3c是在流出道发育过程中介导cNCCs和SHF之间相互作用的一个候选因子。Foxc1/c2直接激活流出道中Sema3c的转录，然而，作为关键的SHF转录因子Tbx1的亚效等位基因，导致Sema3c在咽弓区域的异位表达。Fgf8是Tbx1的下游分泌因子，它通过激活ERK1/2信号通路抑制cNCCs中Sema3c的表达。阻断FGF8会导致SEMA3C的异位表达以及cNCCs的迁移缺陷，从而导致鸡咽弓发育异常。这些结果表明，Sema3c适当的时空表达分别受到Foxc1/c2的正向调节和Tbx1 - Fgf8级联的负向调节，这对于cNCCs和SHF之间的相互作用至关重要，这种相互作用能正确引导cNCCs向由SHF衍生细胞组成的流出道迁移。
The cardiac neural crest cells (cNCCs) and the second heart field (SHF) play key roles in development of the cardiac outflow tract (OFT) for establishment of completely separated pulmonary and systemic circulations in vertebrates. A neurovascular guiding factor, Semaphorin 3c (Sema3c), is required for the development of the OFT, however, its regulation of the interaction between cNCCs and SHF remains to be determined. Here, we show that a Sema3c is a candidate that mediates interaction between cNCCs and the SHF during development of the OFT. Foxc1/c2 directly activates the transcription of Sema3c in the OFT, whereas, a hypomorph of Tbx1, a key SHF transcription factor, resulted in the ectopic expression of Sema3c in the pharyngeal arch region. Fgf8, a downstream secreted factor of Tbx1, inhibited the expression of Sema3c in cNCCs via activation of ERK1/2 signaling. Blocking of FGF8 caused ectopic expression of SEMA3C and a migration defect of cNCCs, resulting in abnormal chick pharyngeal arch development. These results suggest that proper spatio-temporal expression of Sema3c, regulated positively by Foxc1/c2 and negatively by the Tbx1-Fgf8 cascade, respectively, is essential for the interaction between cNCCs and the SHF that correctly navigates cNCCs towards the OFT, composed of SHF-derived cells.
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影响因子：
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作者：
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通讯作者：
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