A novel embryonic nestin-expressing radial glia-like progenitor gives rise to zonally restricted olfactory and vomeronasal neurons
A novel embryonic nestin-expressing radial glia-like progenitor gives rise to zonally restricted olfactory and vomeronasal neurons
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DOI：
10.1523/jneurosci.5566-07.2008
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发表时间：
2008-04-16
影响因子：
5.3
通讯作者：
Roskams, A. Jane
中科院分区：
文献类型：
--
作者：
Murdoch, Barbara;Roskams, A. Jane
小鼠嗅上皮（OE）在整个发育和成年期都维持持续的神经发生。尽管如此，不同胚胎 OE 祖细胞的身份和起源、它们的时空诱导以及对发育过程中模式形成的贡献仍有待描述。在这里，我们发现胚胎 OE 含有一种新型的表达巢蛋白的放射状胶质细胞样祖细胞 (RGLP)，在成人 OE 中未发现，其在抗原上与胚胎 CNS 放射状胶质细胞不同。使用三种不同报告基因的 Nestin-cre 介导的谱系追踪表明，只有表达巢蛋白的 RGLP 的一个亚群激活“中枢神经系统特异性”巢蛋白调节元件，并在 OE 区域 1 中产生空间受限的嗅觉受体神经元 (ORN)，以及仅限于 VR1 区域的犁鼻受体神经元。这种转基因激活细胞的背侧内侧限制也出现在 Nestin-GFP 转基因小鼠的胚胎 OE 中，其中在 GFP + Mash1 + 神经元祖细胞亚群中发现了绿色荧光蛋白 (GFP)，尽管内源性 Nestin 表达存在于整个 OE 的 RGLP 中。胚胎OE祖细胞在体外产生三种生物学上不同的集落亚型，其中一个亚群在体外集落形成过程中包括表达巢蛋白的RGLP。当从 Nestin-cre/ZEG 小鼠中产生时，神经源性集落也会产生 GFP + Mash1 + 祖细胞和 ORN。因此，我们鉴定了一种新的神经源性前体，即 OE 和犁鼻器 (VNO) 的 RGLP，并为 OE 和 VNO 发育过程中不同祖细胞的起源和时空潜力的内在差异提供了第一个证据。
Persistent neurogenesis is maintained throughout development and adulthood in the mouse olfactory epithelium (OE). Despite this, the identity and origin of different embryonic OE progenitors, their spatiotemporal induction and contribution to patterning during development, has yet to be delineated. Here, we show that the embryonic OE contains a novel nestin-expressing radial glia-like progenitor (RGLP) that is not found in adult OE, which is antigenically distinct from embryonic CNS radial glia. Nestin-cre-mediated lineage tracing with three different reporters reveals that only a subpopulation of nestin- expressing RGLPs activate "CNS-specific" nestin regulatory elements, and produce spatially restricted olfactory receptor neurons ( ORNs) in zone 1 of the OE, and vomeronasal receptor neurons restricted to the VR1 zone. This dorsal-medial restriction of transgene-activating cells is also seen in the embryonic OE of Nestin-GFP transgenic mice, in which green fluorescent protein (GFP) is found in a subpopulation of GFP + Mash1 + neuronal progenitors, despite the fact that endogenous Nestin expression is found in RGLPs throughout the OE. Embryonic OE progenitors produce three biologically distinct colony subtypes in vitro, a subpopulation of which include nestin- expressing RGLPs during in vitro colony formation. When generated from Nestin-cre/ZEG mice, neurogenic colonies also produce GFP + Mash1 + progenitors and ORNs. We thus identify a novel neurogenic precursor, the RGLP of the OE and vomeronasal organ (VNO), and provide the first evidence for intrinsic differences in the origin and spatiotemporal potential of distinct progenitors during development of the OE and VNO.