Cis-regulatory analysis of nodal and maternal control of dorsal-ventral axis formation by Univin, a TGF-β related to Vg1
Cis-regulatory analysis of nodal and maternal control of dorsal-ventral axis formation by Univin, a TGF-β related to Vg1
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DOI：
10.1242/dev.007799
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发表时间：
2007-10-15
期刊：
影响因子：
4.6
通讯作者：
Lepage, Thierry
中科院分区：
文献类型：
--
作者：
Range, Ryan;Lapraz, Francois;Lepage, Thierry
TGF- β家族成员Nodal对海胆胚胎背腹轴的发育至关重要，但调控其表达的分子因子尚不清楚。节点启动子的分析是一个很好的切入点，以确定这些因素和剖析驱动背-腹轴规范的调控逻辑。利用系统发育足迹，我们描绘了位于节点启动子的5 '区域和内含子中的两个调节区域，这两个区域是正确的空间表达和自动调节所必需的。5 '调控区包含同源域、bZIP、Oct、Tcf/ left、Sox和Smad转录因子的必需结合位点，以及一个可能与Myb相关的未知空间抑制因子的结合位点。在其发生后不久，淋巴结的表达就迫切需要淋巴结的自我调节和母体TGF- β Univin的信号传导。我们发现Univin与Vg1相关，Nodal和Univin都通过Alk4/ 5/ 7进行信号传递，并且Univin的合子表达与Nodal一样依赖于SoxB1功能和Tcf/ β - catenin信号传导。这项工作表明，Tcf、SoxB1和Univin在海胆的节点表达调控中发挥了重要作用，并表明一些控制节点表达的调控相互作用早于脊索动物。这些数据与母体TGF- β与母体转录因子和空间抑制因子协同作用建立海胆胚胎背-腹侧轴的节点调节模型一致。
The TGF- beta family member Nodal is essential for specification of the dorsal- ventral axis of the sea urchin embryo, but the molecular factors regulating its expression are not known. Analysis of the nodal promoter is an excellent entry point to identify these factors and to dissect the regulatory logic driving dorsal- ventral axis specification. Using phylogenetic footprinting, we delineated two regulatory regions located in the 5 ' region of the nodal promoter and in the intron that are required for correct spatial expression and for autoregulation. The 5 ' regulatory region contains essential binding sites for homeodomain, bZIP, Oct, Tcf/ Lef, Sox and Smad transcription factors, and a binding site for an unidentified spatial repressor possibly related to Myb. Soon after its initiation, nodal expression critically requires autoregulation by Nodal and signaling by the maternal TGF- beta Univin. We show that Univin is related to Vg1, that both Nodal and Univin signal through Alk4/ 5/ 7, and that zygotic expression of univin, like that of nodal, is dependent on SoxB1 function and Tcf/ beta- catenin signaling. This work shows that Tcf, SoxB1 and Univin play essential roles in the regulation of nodal expression in the sea urchin and suggests that some of the regulatory interactions controlling nodal expression predate the chordates. The data are consistent with a model of nodal regulation in which a maternal TGF- beta acts in synergy with maternal transcription factors and with spatial repressors to establish the dorsal- ventral axis of the sea urchin embryo.