Department of Molecular Genetics and Microbiology and The Genetics Institute, University of Florida, College of Medicine, Gainesville, FL 32610, USA.
Mech Dev. 2012 Sep-Dec;129(9-12):255-62. doi: 10.1016/j.mod.2012.07.003. Epub 2012 Jul 25.
The intervertebral discs, located between adjacent vertebrae, are required for stability of the spine and distributing mechanical load throughout the vertebral column. All cell types located in the middle regions of the discs, called nuclei pulposi, are derived from the embryonic notochord. Recently, it was shown that the hedgehog signaling pathway plays an essential role during formation of nuclei pulposi. However, during the time that nuclei pulposi are forming, Shh is expressed in both the notochord and the nearby floor plate. To determine the source of SHH protein sufficient for formation of nuclei pulposi we removed Shh from either the floor plate or the notochord using tamoxifen-inducible Cre alleles. Removal of Shh from the floor plate resulted in phenotypically normal intervertebral discs, indicating that Shh expression in this tissue is not required for disc patterning. In addition, embryos that lacked Shh in the floor plate had normal vertebral columns, demonstrating that Shh expression in the notochord is sufficient for pattering the entire vertebral column. Removal of Shh from the notochord resulted in the absence of Shh in the floor plate, loss of intervertebral discs and vertebral structures. These data indicate that Shh expression in the notochord is sufficient for patterning of the intervertebral discs and the vertebral column.
椎间盘位于相邻椎骨之间,是脊柱稳定性和整个脊柱机械负荷分布所必需的。位于椎间盘中部的所有细胞类型,称为髓核,均来源于胚胎脊索。最近表明, hedgehog 信号通路在髓核形成过程中发挥着重要作用。然而,在髓核形成期间,Shh 在脊索和附近的基板中均有表达。为了确定形成髓核所需的 SHH 蛋白的来源,我们使用他莫昔芬诱导型 Cre 等位基因去除基板或脊索中的 Shh。从基板中去除 Shh 导致椎间盘表型正常,表明该组织中 Shh 的表达对于椎间盘的模式形成不是必需的。此外,基板中缺乏 Shh 的胚胎具有正常的椎骨,表明脊索中 Shh 的表达足以对整个椎骨进行模式形成。从脊索中去除 Shh 导致基板中 Shh 的缺失,椎间盘和椎骨结构的丧失。这些数据表明,脊索中 Shh 的表达足以对椎间盘和椎骨进行模式形成。