Gli2 and Gli3 play distinct roles in the dorsoventral patterning of the mouse hindbrain
Gli2 and Gli3 play distinct roles in the dorsoventral patterning of the mouse hindbrain
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DOI：
10.1016/j.ydbio.2006.08.005
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发表时间：
2007-02-01
影响因子：
2.7
通讯作者：
Hui, Chi-chung
中科院分区：
文献类型：
--
作者：
Lebel, Melanie;Mo, Rong;Hui, Chi-chung
Sonic Hedgehog（Shh）信号通过调节神经模式化基因的表达在发育中的神经管的背腹（DV）模式化过程中起关键作用。Gli 2和Gli 3的重叠激活功能已被证明是腹侧脊髓中运动神经元发育和正确神经模式所需的。然而，Gli 2和Gli 3在腹侧后脑发育中的作用尚不清楚。本文研究了Shh（-/-）、Gli 2（-/-）和Gli 3（-/-）胚胎后脑的DV模式，发现Gli 2和Gli 3的作用不仅在后脑和脊髓之间不同，而且在后脑的不同吻尾水平也不同。值得注意的是，GU 2（-/-）胚胎的前后脑显示出与Shh（-/-）胚胎中观察到的一样严重的腹侧图案化缺陷，这表明与脊髓和后后脑不同，Gli 3不能补偿前后脑Shh依赖性腹侧图案化中Gli 2激活剂功能的丧失。Gli 3的缺失还导致前后脑中明显的图案缺陷，包括Nkx6.1表达的背侧扩张。此外，我们表明，腹侧图案的菱形4是受损失的Gli 2功能揭示了不同的要求Gli蛋白在这个菱形的影响较小。两者合计，这些观察结果表明，Gli 2和Gli 3执行菱体特异性功能，在DV图案的后脑。(c)2006年爱思唯尔公司All rights reserved.
Sonic Hedgehog (Shh) signaling plays a critical role during dorsoventral (DV) patterning of the developing neural tube by modulating the expression of neural patterning genes. Overlapping activator functions of Gli2 and Gli3 have been shown to be required for motoneuron development and correct neural patterning in the ventral spinal cord. However, the role of Gli2 and Gli3 in ventral hindbrain development is unclear. In this paper, we have examined DV patterning of the hindbrain of Shh(-/-), Gli2(-/-) and Gli3(-/-) embryos, and found that the respective role of Gli2 and Gli3 is not only different between the hindbrain and spinal cord, but also at distinct rostrocaudal levels of the hindbrain. Remarkably, the anterior hindbrain of GU2(-/-) embryos displays ventral patterning defects as severe as those observed in Shh(-/-) embryos suggesting that, unlike in the spinal cord and posterior hindbrain, Gli3 cannot compensate for the loss of Gli2 activator function in Shh-dependent ventral patterning of the anterior hindbrain. Loss of Gli3 also results in a distinct patterning defect in the anterior hindbrain, including dorsal expansion of Nkx6.1 expression. Furthermore, we demonstrate that ventral patterning of rhombomere 4 is less affected by loss of Gli2 function revealing a different requirement for Gli proteins in this rhombomere. Taken together, these observations indicate that Gli2 and Gli3 perform rhombomere-specific function during DV patterning of the hindbrain. (c) 2006 Elsevier Inc. All rights reserved.