Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice.
Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice.
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DOI：
10.1097/brs.0b013e318210eec4
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发表时间：
2011-11-15
期刊：
影响因子：
3
通讯作者：
Harfe BD
中科院分区：
文献类型：
--
作者：
Maier JA;Harfe BD
使用Shhcre和R26 R等位基因在GDF-5缺失小鼠中体内确定小鼠胚胎脊索向髓核的转变（“命运定位”）。确定胚胎脊索的异常髓核形成是否是Gdf-5基因敲除小鼠成年髓核缺陷的原因。椎间盘的发育、维持和退变尚不清楚。以前，我们证明了正常小鼠成年髓核中的所有细胞都来自胚胎脊索。据报道，Gdf-5缺失小鼠含有椎间盘，其中髓核异常。目前尚不清楚Gdf-5基因敲除小鼠的椎间盘缺陷是否是在胚胎发育期间脊索髓核形成期间出现的，还是由于髓核的进行性出生后变性引起的。GDF-5 mRNA的表达进行了检查，在光盘的野生型胚胎的RNA原位杂交，以确定何时何地该基因表达。为了检查Gdf-5缺失小鼠中的髓核形成，在新生和24周龄小鼠中分析其中标记胚胎脊索细胞的椎间盘。我们的Gdf-5 mRNA原位实验确定，该基因是本地化的纤维环，而不是髓核在小鼠胚胎。脊索命运定位实验显示Gdf-5缺失小鼠中的脊索细胞正确形成髓核。我们的数据表明，在成年GDF-5基因敲除小鼠髓核中报告的缺陷并不是由胚胎脊索的异常模式造成的。使用小鼠等位基因来标记产生存在于成年髓核中的所有细胞类型的细胞，将允许详细检查已报道含有椎间盘缺陷的其他小鼠突变体中的椎间盘形成。
The transition of the mouse embryonic notochord into nuclei pulposi was determined (“fate mapped”) in vivo in GDF-5 null mice using the Shhcre and R26R alleles. To determine if abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5 null mice. The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5 null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5 null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or resulted from progressive postnatal degeneration of nuclei pulposi. Gdf-5 mRNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5 null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24 week old mice. Our Gdf-5 mRNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate mapping experiments revealed that notochord cells in Gdf-5 null mice correctly form nuclei pulposi. Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5 null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects.