Lebel Mélanie, Mo Rong, Shimamura Kenji, Hui Chi-chung
Program in Developmental Biology, The Hospital for Sick Children, Room 13-314, Toronto Medical Discovery Tower, Ontario, Canada.
Dev Biol. 2007 Feb 1;302(1):345-55. doi: 10.1016/j.ydbio.2006.08.005. Epub 2006 Aug 9.
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 Gli2(-/-) 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.
音猬因子（Shh）信号通路通过调节神经模式形成基因的表达，在发育中神经管的背腹（DV）模式形成过程中发挥关键作用。Gli2和Gli3的重叠激活功能已被证明是运动神经元发育和脊髓腹侧正确神经模式形成所必需的。然而，Gli2和Gli3在腹侧后脑发育中的作用尚不清楚。在本文中，我们研究了Shh（-/-）、Gli2（-/-）和Gli3（-/-）胚胎后脑的DV模式形成，发现Gli2和Gli3各自的作用不仅在后脑和脊髓之间不同，而且在不同的后脑头尾水平上也不同。值得注意的是，Gli2（-/-）胚胎的前脑显示出与Shh（-/-）胚胎中观察到的一样严重的腹侧模式形成缺陷，这表明与脊髓和后脑后部不同，在Shh依赖的前脑腹侧模式形成中，Gli3不能补偿Gli2激活功能的丧失。Gli3的缺失也导致前脑出现明显的模式形成缺陷，包括Nkx6.1表达的背侧扩展。此外，我们证明，菱形节4的腹侧模式形成受Gli2功能丧失的影响较小，这揭示了该菱形节中Gli蛋白的不同需求。综上所述，这些观察结果表明，Gli2和Gli3在后脑DV模式形成过程中执行菱形节特异性功能。
