Dynamic interactions between intermediate neurogenic progenitors and radial glia in embryonic mouse neocortex: potential role in Dll1-Notch signaling.
Dynamic interactions between intermediate neurogenic progenitors and radial glia in embryonic mouse neocortex: potential role in Dll1-Notch signaling.
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DOI：
10.1523/jneurosci.0791-13.2013
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发表时间：
2013-05-22
期刊：
影响因子：
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通讯作者：
Hevner RF
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作者：
Nelson BR;Hodge RD;Bedogni F;Hevner RF
哺乳动物新皮质祖细胞龛由神经上皮细胞、放射状胶质细胞（RG）和中间神经源性祖细胞（INPs）组成。此前，活细胞成像实验已被证明在识别这些不同的祖细胞群体，特别是INPs方面至关重要，INPs通过在分化成新神经元之前进行额外的增殖来放大神经输出。INPs还通过作为Delta样1（Dll 1）的来源向RG池提供反馈，Dll 1是激活相邻细胞中Notch信号传导的关键配体，这是一种众所周知的维持RG身份的机制。虽然在分子水平上对Dll 1-Notch信号传导了解很多，但对这种细胞-细胞接触依赖性反馈如何在细胞水平上传递知之甚少。为了研究RG和INPs如何相互作用以传递Notch信号，我们使用高分辨率活细胞多光子显微镜（MPM）直接观察细胞相互作用和动力学，结合胚胎小鼠器官型脑切片中新皮质神经干细胞龛中Notch通路特异性报告基因。我们发现INPs和RG通过动态和短暂的伸长过程相互作用，一些明显的长程（从脑室下区延伸到脑室区），和一些短程（丝状伪足样）。RG和INPs的基因表达谱显示了进一步的祖细胞多样化，包括Hes 1+和/或Hes 5 + RG和Dll 1+和/或Dll 3 + INPs的不同亚群。因此，胚胎祖细胞生态位包括动态细胞-细胞相互作用的网络，利用Notch信号分子的不同组合来维持祖细胞库并可能使其多样化。
The mammalian neocortical progenitor cell niche is composed of a diverse repertoire of neuroepithelial cells, radial glia (RG), and intermediate neurogenic progenitors (INPs). Previously, live-cell imaging experiments have proved crucial in identifying these distinct progenitor populations, especially INPs, which amplify neural output by undergoing additional rounds of proliferation before differentiating into new neurons. INPs also provide feedback to the RG pool by serving as a source of Delta-like 1 (Dll1), a key ligand for activating Notch signaling in neighboring cells, a well-known mechanism for maintaining RG identity. While much is known about Dll1-Notch signaling at the molecular level, little is known about how this cell-cell contact dependent feedback is transmitted at the cellular level. To investigate how RG and INPs might interact to convey Notch signals, we used high-resolution live-cell multiphoton microscopy (MPM) to directly observe cellular interactions and dynamics, in conjunction with Notch-pathway specific reporters in the neocortical neural stem cell niche in organotypic brain slices from embryonic mice. We found that INPs and RG interact via dynamic and transient elongate processes, some apparently long-range (extending from the subventricular zone to the ventricular zone), and some short-range (filopodia-like). Gene expression profiling of RG and INPs revealed further progenitor cell diversification, including different subpopulations of Hes1+ and/or Hes5+ RG, and Dll1+ and/or Dll3+ INPs. Thus, the embryonic progenitor niche includes a network of dynamic cell-cell interactions, utilizing different combinations of Notch signaling molecules to maintain and likely diversify progenitor pools.