Ray Heather J, Niswander Lee A
Department of Pediatrics, Cell Biology Stem Cells and Development Graduate Program, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO 80045, USA.
Department of Pediatrics, Cell Biology Stem Cells and Development Graduate Program, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO 80045, USA.
Dev Biol. 2016 Aug 15;416(2):279-85. doi: 10.1016/j.ydbio.2016.06.030. Epub 2016 Jun 22.
The embryonic brain and spinal cord initially form through the process of neural tube closure (NTC). NTC is thought to be highly similar between rodents and humans, and studies of mouse genetic mutants have greatly increased our understanding of the molecular basis of NTC with relevance for human neural tube defects. In addition, studies using amphibian and chick embryos have shed light into the cellular and tissue dynamics underlying NTC. However, the dynamics of mammalian NTC has been difficult to study due to in utero development until recently when advances in mouse embryo ex vivo culture techniques along with confocal microscopy have allowed for imaging of mouse NTC in real time. Here, we have performed live imaging of mouse embryos with a particular focus on the non-neural ectoderm (NNE). Previous studies in multiple model systems have found that the NNE is important for proper NTC, but little is known about the behavior of these cells during mammalian NTC. Here we utilized a NNE-specific genetic labeling system to assess NNE dynamics during murine NTC and identified different NNE cell behaviors as the cranial region undergoes NTC. These results bring valuable new insight into regional differences in cellular behavior during NTC that may be driven by different molecular regulators and which may underlie the various positional disruptions of NTC observed in humans with neural tube defects.
胚胎期的脑和脊髓最初是通过神经管闭合(NTC)过程形成的。人们认为啮齿动物和人类的神经管闭合过程高度相似,对小鼠基因变异体的研究极大地增进了我们对与人类神经管缺陷相关的神经管闭合分子基础的理解。此外,利用两栖动物和鸡胚胎进行的研究揭示了神经管闭合背后的细胞和组织动态变化。然而,由于胚胎在子宫内发育,哺乳动物神经管闭合的动态变化一直难以研究,直到最近小鼠胚胎体外培养技术的进步以及共聚焦显微镜的应用使得实时成像小鼠神经管闭合成为可能。在此,我们对小鼠胚胎进行了活体成像,特别关注非神经外胚层(NNE)。此前在多个模型系统中的研究发现,非神经外胚层对正常的神经管闭合很重要,但对于这些细胞在哺乳动物神经管闭合过程中的行为了解甚少。在这里,我们利用一种非神经外胚层特异性基因标记系统来评估小鼠神经管闭合过程中非神经外胚层的动态变化,并确定了在颅部区域发生神经管闭合时非神经外胚层细胞的不同行为。这些结果为神经管闭合过程中细胞行为的区域差异带来了有价值的新见解,这种差异可能由不同的分子调节因子驱动,并且可能是人类神经管缺陷中观察到的各种神经管闭合位置异常的基础。