Midbrain-Hindbrain Boundary Morphogenesis: At the Intersection of Wnt and Fgf Signaling.
Midbrain-Hindbrain Boundary Morphogenesis: At the Intersection of Wnt and Fgf Signaling.
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DOI：
10.3389/fnana.2017.00064
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发表时间：
2017
影响因子：
2.9
通讯作者：
Lekven AC
中科院分区：
文献类型：
--
作者：
Gibbs HC;Chang-Gonzalez A;Hwang W;Yeh AT;Lekven AC
中脑和后脑交界处的神经管收缩是脊椎动物胚胎的保守特征。这种收缩是中脑-后脑边界(MHB)的一个明显特征，MHB是一个信号中心，排列相邻的中脑和头端后脑，并在早期神经板的两个基因表达结构域的交界处形成：前OTX2/wnt1阳性区域和后GBX/Fgf8阳性区域。OTX2和GBX基因编码相互抑制的转录因子，在其表达界面形成谱系限制边界。WNT和FGF基因形成了一个相互依赖的反馈系统，分别将它们的表达结构域维持在边界的OTX2或GBX一侧。在这些保守的基因表达结构域建立后，收缩形态发生，而它们之间的相互作用维持了它们的表达模式；因此，斑马鱼的突变研究表明，收缩形态发生应该被认为是MHB发育的一个独特阶段。我们使用一个由保守的wnt1增强子驱动的报告来观察前边界细胞，分析了Fgf8功能丧失的斑马鱼胚胎中MHB的形态发生。我们发现，Fgf8功能丧失导致边界后wnt1报告表达重新激活，同时前边界细胞中wnt1报告失活，并且这些事件与边界收缩的松弛有关。考虑到其他与Wnt和Fgf表达相关的结果，我们认为维持一个活跃的Wnt-Fgf反馈环是驱动MHB收缩形态发生的关键因素。
A constriction in the neural tube at the junction of the midbrain and hindbrain is a conserved feature of vertebrate embryos. The constriction is a defining feature of the midbrain-hindbrain boundary (MHB), a signaling center that patterns the adjacent midbrain and rostral hindbrain and forms at the junction of two gene expression domains in the early neural plate: an anterior otx2/wnt1 positive domain and a posterior gbx/fgf8 positive domain. otx2 and gbx genes encode mutually repressive transcription factors that create a lineage restriction boundary at their expression interface. Wnt and Fgf genes form a mutually dependent feedback system that maintains their expression domains on the otx2 or gbx side of the boundary, respectively. Constriction morphogenesis occurs after these conserved gene expression domains are established and while their mutual interactions maintain their expression pattern; consequently, mutant studies in zebrafish have led to the suggestion that constriction morphogenesis should be considered a unique phase of MHB development. We analyzed MHB morphogenesis in fgf8 loss of function zebrafish embryos using a reporter driven by the conserved wnt1 enhancer to visualize anterior boundary cells. We found that fgf8 loss of function results in a re-activation of wnt1 reporter expression posterior to the boundary simultaneous with an inactivation of the wnt1 reporter in the anterior boundary cells, and that these events correlate with relaxation of the boundary constriction. In consideration of other results that correlate the boundary constriction with Wnt and Fgf expression, we propose that the maintenance of an active Wnt-Fgf feedback loop is a key factor in driving the morphogenesis of the MHB constriction.
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影响因子：
4.6
作者：
Foucher, I;Mione, M;Houart, C
通讯作者：
Houart, C
影响因子：
2
作者：
Filas BA;Oltean A;Majidi S;Bayly PV;Beebe DC;Taber LA
通讯作者：
Taber LA
影响因子：
2.5
作者：
Green, David;Whitener, Amy E.;Lekven, Arne C.
通讯作者：
Lekven, Arne C.
DOI：
10.1083/jcb.201507108
发表时间：
2015-11-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Jontes JD
影响因子：
2.5
作者：
Babb, SG;Barnett, J;Marrs, JA
通讯作者：
Marrs, JA