Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation.

Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation.
复制标题

SRGAP2 人类特异性旁系同源物对 SRGAP2 功能的抑制可在脊柱成熟过程中诱导幼态持续

DOI:
10.1016/j.cell.2012.03.034
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发表时间:
2012-05-11
期刊:
影响因子:
64.5
通讯作者:
Polleux F
Polleux F
中科院分区:
生物学1区
文献类型:
--
作者:
Charrier C;Joshi K;Coutinho-Budd J;Kim JE;Lambert N;de Marchena J;Jin WL;Vanderhaeghen P;Ghosh A;Sassa T;Polleux F

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结构基因组变异是进化的主要驱动力,在人类与非人类灵长类动物分离的过程中,人类谱系中出现了大片段基因复制的爆发。SRGAP2,一个最近与新皮质发育有关的基因,经历了两次人类特异性的复制。在这里,我们发现两个复制(SRGAP2B和SRGAP2C)都是部分的,并且编码截断的F-BAR结构域。SRGAP2C在发育和成人大脑中表达,并与祖先SRGAP2二聚体抑制其功能。在小鼠新皮质中,SRGAP2促进脊柱成熟并限制脊柱密度。SRGAP2C表型表达反映SRGAP2缺陷。它是持续径向迁移的基础,并导致人类特有特征的出现,包括脊柱成熟期间的幼变和长脊柱密度的增加。这些结果表明,SRGAP2的人类特异性类似物对其功能的抑制有助于人类新皮层的进化,并在人类大脑发育过程中发挥重要作用。
Structural genomic variations represent a major driving force of evolution and a burst of large segmental gene duplications occurred in the human lineage during its separation from non-human primates. SRGAP2, a gene recently implicated in neocortical development, has undergone two human-specific duplications. Here we find that both duplications (SRGAP2B and SRGAP2C) are partial and encode a truncated F-BAR domain. SRGAP2C is expressed in the developing and adult human brain and dimerizes with ancestral SRGAP2 to inhibit its function. In the mouse neocortex, SRGAP2 promotes spine maturation and limits spine density. Expression of SRGAP2C phenocopies SRGAP2 deficiency. It underlies sustained radial migration and leads to the emergence of human-specific features, including neoteny during spine maturation and increased density of longer spines. These results suggest that inhibition of SRGAP2 function by its human-specific paralogs has contributed to the evolution of the human neocortex and plays an important role during human brain development.
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