Pax6 regulates boundary-cell specification in the rat hindbrain
Pax6 regulates boundary-cell specification in the rat hindbrain
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DOI：
10.1016/j.mod.2011.04.001
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发表时间：
2011-05
影响因子：
2.6
通讯作者：
Masanori Takahashi;N. Osumi
中科院分区：
文献类型：
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作者：
Masanori Takahashi;N. Osumi
脊椎动物神经上皮可分为非边界区和边界区。边界区域作为区域规范和邻近非边界区域神经发生的信号中心。一个重要的问题是在大脑发育过程中如何指定和维持边界区域。在这项研究中，我们报道了Pax6，一个同源结构域转录因子，调节发育中的大鼠后脑的大鼠双形体之间的边界细胞规范。我们比较了plzf （Zbtb16）、Ring1A（Ring1）、Wnt5a和cadherin7（Cdh7）四种边界细胞标记在野生型和pax6功能缺失突变后脑中的表达模式，发现Zbtb16、Ring1和wnt5a在rhomomere边界的表达下调，而ecdh7在pax6突变后脑的非边界区域的表达上调。形态学观察表明，pax6突变体后脑的边界区更大，边界区与非边界区之间的界面模糊。我们还发现pax6突变后脑的边界细胞有异位神经元分化。此外，我们观察到pax6突变体后脑边界区域的es5下调，neurogenin2 （Neurog2）上调。由于pax6基因已被证明通过抑制前神经基因来抑制神经元分化，因此pax6可能通过这一途径阻止边界细胞中的神经发生。综上所述，Pax6似乎是协调边界细胞规范和减少后脑边界区域内神经发生所必需的。
The vertebrate neuroepithelium can be subdivided into non-boundary and boundary regions. The boundary regions act as signaling centers for regional specification and neurogenesis in the neighboring non-boundary regions. An important question is how boundary regions are specified and maintained during brain development. In this study, we report that Pax6, a homeodomain transcription factor, regulates boundary-cell specification between rhombomeres of the developing rat hindbrain. We compared expression patterns of four boundary-cell markers, includingPLZF(Zbtb16), Ring1A(Ring1),Wnt5a,andcadherin7(Cdh7), in wild-type andPax6loss-of-function mutant hindbrains and found that the expression ofZbtb16,Ring1, andWnt5awas down-regulated in the rhombomere boundaries, whileCdh7expression was up-regulated in the non-boundary regions of thePax6mutant hindbrain. Morphological observations revealed that the boundary regions were larger and that the interface between the boundary and non-boundary regions was obscured in thePax6mutant hindbrain. We also found ectopic neuronal differentiation in the boundary cells of thePax6mutant hindbrain. In addition, we observed thatHes5was down-regulated and thatNeurogenin2(Neurog2) was up-regulated in the boundary regions of thePax6mutant hindbrain. BecauseHesgenes have been shown to inhibit neuronal differentiation by repressing proneural genes,Pax6may act through this pathway to prevent neurogenesis in the boundary cells. Taken together, Pax6 seems to be required for coordinating boundary-cell specification and reducing neurogenesis within the hindbrain boundary region.