Young Kaylene M, Fogarty Matthew, Kessaris Nicoletta, Richardson William D
Wolfson Institute for Biomedical Research and Department of Biology, University College London, London WC1E 6BT, United Kingdom.
J Neurosci. 2007 Aug 1;27(31):8286-96. doi: 10.1523/JNEUROSCI.0476-07.2007.
We determined the embryonic origins of adult forebrain subventricular zone (SVZ) stem cells by Cre-lox fate mapping in transgenic mice. We found that all parts of the telencephalic neuroepithelium, including the medial ganglionic eminence and lateral ganglionic eminence (LGE) and the cerebral cortex, contribute multipotent, self-renewing stem cells to the adult SVZ. Descendants of the embryonic LGE and cortex settle in ventral and dorsal aspects of the dorsolateral SVZ, respectively. Both populations contribute new (5-bromo-2'-deoxyuridine-labeled) tyrosine hydroxylase- and calretinin-positive interneurons to the adult olfactory bulb. However, calbindin-positive interneurons in the olfactory glomeruli were generated exclusively by LGE-derived stem cells. Thus, different SVZ stem cells have different embryonic origins, colonize different parts of the SVZ, and generate different neuronal progeny, suggesting that some aspects of embryonic patterning are preserved in the adult SVZ. This could have important implications for the design of endogenous stem cell-based therapies in the future.
我们通过转基因小鼠中的Cre-lox命运图谱确定了成年前脑脑室下区（SVZ）干细胞的胚胎起源。我们发现，端脑神经上皮的所有部分，包括内侧神经节隆起和外侧神经节隆起（LGE）以及大脑皮层，都为成年SVZ贡献多能、自我更新的干细胞。胚胎LGE和皮层的后代分别定居在背外侧SVZ的腹侧和背侧。这两个群体都为成年嗅球贡献新的（5-溴-2'-脱氧尿苷标记的）酪氨酸羟化酶和钙视网膜蛋白阳性中间神经元。然而，嗅小球中的钙结合蛋白阳性中间神经元仅由LGE衍生的干细胞产生。因此，不同的SVZ干细胞具有不同的胚胎起源，定殖在SVZ的不同部位，并产生不同的神经元后代，这表明胚胎模式形成的某些方面在成年SVZ中得以保留。这可能对未来基于内源性干细胞的治疗设计具有重要意义。
