Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex.
Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex.
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DOI：
10.1038/nature13973
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发表时间：
2014-11-13
期刊：
影响因子：
64.8
通讯作者：
Oldham, Michael C.
中科院分区：
文献类型：
--
作者：
Lui, Jan H.;Nowakowski, Tomasz J.;Pollen, Alex A.;Javaherian, Ashkan;Kriegstein, Arnold R.;Oldham, Michael C.
人类新大脑皮层的进化扩张是我们许多独特心理能力的基础。这种扩张归因于新皮质发育过程中放射状胶质细胞(RG；即神经干细胞)增殖能力的增强以及它们在脑室周围壁龛中的弥散。这种适应可能是通过RG中基因表达的变化而进化的。然而，RG基因在人类和其他物种之间的表达是否或如何差异尚不清楚。在这里，我们表明，人类和小鼠新皮质RG的转录图谱在神经发生过程中广泛保守，但在特定的信号通路上存在分歧。通过分析不同物种之间的差异基因共表达关系，我们证明了生长因子PDGFD在人类而不是小鼠的皮质生成中由RG特异性表达。我们进一步证明，PDGFD的同源受体PDGFR？的表达结构域在进化上是不同的，在人背侧新皮质生发区高表达，而在小鼠中不表达。在切片培养中药物抑制PDGFD/PDGFR？信号可阻止人新皮质RG的正常细胞周期进程，但不能阻止小鼠。相反，在发育中的小鼠新皮质注射重组PDGFD或异位表达有成分活性的PDGFR？可增加RG的比例及其在脑室下的弥散度。这些发现强调了PDGFD/PDGFRç信号对人类新皮质发育的需求，并表明RG局部产生的生长因子支持大脑物种扩大的生发区和祖细胞的异质性。
Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential, of radial glia (RG; i.e. neural stem cells) and their subventricular dispersion from the periventricular niche during neocortical development. Such adaptations may have evolved through gene expression changes in RG. However, whether or how RG gene expression varies between humans and other species is unknown. Here we show that the transcriptional profiles of human and mouse neocortical RG are broadly conserved during neurogenesis, yet diverge for specific signaling pathways. By analyzing differential gene coexpression relationships between the species, we demonstrate that the growth factor PDGFD is specifically expressed by RG in human, but not mouse, corticogenesis. We further show that the expression domain of PDGFRß, the cognate receptor for PDGFD, is evolutionarily divergent, with high expression in the germinal region of dorsal human neocortex but not in the mouse. Pharmacological inhibition of PDGFD/PDGFRß signaling in slice culture prevents normal cell cycle progression of neocortical RG in human, but not mouse. Conversely, injection of recombinant-PDGFD or ectopic expression of constitutively active PDGFRß in developing mouse neocortex increases the proportion of RG and their subventricular dispersion. These findings highlight the requirement of PDGFD/PDGFRß signaling for human neocortical development and suggest that local production of growth factors by RG supports the expanded germinal region and progenitor heterogeneity of species with large brains.
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影响因子：
16.2
作者：
Geschwind DH;Rakic P
通讯作者：
Rakic P
GPR56的进化动态替代剪接调节区域脑皮质模式。
DOI：
10.1126/science.1244392
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bae BI;Tietjen I;Atabay KD;Evrony GD;Johnson MB;Asare E;Wang PP;Murayama AY;Im K;Lisgo SN;Overman L;Šestan N;Chang BS;Barkovich AJ;Grant PE;Topçu M;Politsky J;Okano H;Piao X;Walsh CA
通讯作者：
Walsh CA
影响因子：
21.3
作者：
Bergsten, E;Uutela, M;Eriksson, U
通讯作者：
Eriksson, U
影响因子：
64.5
作者：
Lui JH;Hansen DV;Kriegstein AR
通讯作者：
Kriegstein AR
基因共表达网络分析的几何解释。
影响因子：
4.3
作者：
Horvath, Steve;Dong, Jun
通讯作者：
Dong, Jun