Two tcf3 genes cooperate to pattern the zebrafish brain

Two tcf3 genes cooperate to pattern the zebrafish brain
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DOI:
10.1242/dev.00402
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发表时间:
2003-05-01
期刊:
影响因子:
4.6
通讯作者:
Chitnis, A
Chitnis, A
中科院分区:
生物学2区
文献类型:
--
作者:
Dorsky, RI;Itoh, M;Chitnis, A

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尾端化因子在Wnt/ β -连环蛋白信号传导的背景下起作用,诱导发育中的脊椎动物神经系统沿喙尾轴的离散区室的基因表达。在斑马鱼中,尾侧基因的基础抑制是通过Tcf3同源蛋白Headless (Hdl)的功能实现的。在这项研究中,我们发现第二个Tcf3同源物Tcf3b限制了由Hdl功能丧失引起的尾化,尽管这个Lef/Tcf家族成员可以挽救Hdl突变体,但Lefl不能。wnt可以拮抗由Tcf3介导的抑制,这种抑制依赖于Tcf3 β -连环蛋白结合域。由Tcf3功能降低引起的基因表达的系统性变化有助于预测尾状活性梯度的形状,该梯度定义了沿喙尾轴的隔室。此外,Tcf3b在菱形球边界的形态发生中具有第二种独特的作用,表明它控制着大脑发育的多个方面。
Caudalizing factors operate in the context of Wnt/beta-catenin signaling to induce gene expression in discrete compartments along the rostral-caudal axis of the developing vertebrate nervous system. In zebrafish, basal repression of caudal genes is achieved through the function of Headless (Hdl), a Tcf3 homolog. In this study, we show that a second Tcf3 homolog, Tcf3b, limits caudalization caused by loss of Hdl function and although this Lef/Tcf family member can rescue hdl mutants, Lefl cannot. Wnts can antagonize repression mediated by Tcf3 and this derepression is dependent on a Tcf3 beta-catenin binding domain. Systematic changes in gene expression caused by reduced Tcf3 function help predict the shape of a caudalizing activity gradient that defines compartments along the rostral-caudal axis. In addition, Tcf3b has a second and unique role in the morphogenesis of rhombomere boundaries, indicating that it controls multiple aspects of brain development.