Neocortical Layer Formation of Human Developing Brains and Lissencephalies: Consideration of Layer-Specific Marker Expression

Neocortical Layer Formation of Human Developing Brains and Lissencephalies: Consideration of Layer-Specific Marker Expression
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DOI:
10.1093/cercor/bhq125
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发表时间:
2011-03-01
期刊:
影响因子:
3.7
通讯作者:
Itoh, Masayuki
Itoh, Masayuki
中科院分区:
医学2区
文献类型:
--
作者:
Saito, Takashi;Hanai, Sae;Itoh, Masayuki

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为了研究层特异性分子在人类发育中的新皮质中的表达,我们用免疫组织化学方法研究了16例正常对照、3例Miller-Dieker综合征(MDS)、2例X-连锁无性脑伴生殖器异常(XLAG)和4例Fukuyama型先天性肌营养不良(FCMD)患者中央前回背外侧回的额叶新皮质(Tbr1、Foxp1、SATB2、OTX1、CUTL1和CTIP2)。胎儿期观察到第II-IV层有SATB2+细胞,第II-V层有CUTL1+细胞,第V层有Foxp1+细胞,第II或V层有OTX1+细胞,第V层和第VI层有CTIP2+和TBR1+细胞,SATB2+和CUTL1+细胞在出生后3个月才出现,其他标记细胞在出生后消失。MDS和XLAG婴儿的新皮质显示SATB2+、CUTL1+、Foxp1+和TBR1+细胞弥漫分布在上层。在胎儿FCMD新皮质,层特异性标记的神经元位于胶质细胞限制区上方。本研究提供了新的知识,表明这些标记在发育中的人新皮质中的表达模式与在小鼠中的表达模式相似。各种小脑均可见随机迁移形成的异常层状结构。
To investigate layer-specific molecule expression in human developing neocortices, we performed immunohistochemistry of the layer-specific markers (TBR1, FOXP1, SATB2, OTX1, CUTL1, and CTIP2), using frontal neocortices of the dorsolateral precentral gyri of 16 normal controls, aged 19 gestational weeks to 1 year old, lissencephalies of 3 Miller-Dieker syndrome (MDS) cases, 2 X-linked lissencephaly with abnormal genitalia (XLAG) cases, and 4 Fukuyama-type congenital muscular dystrophy (FCMD) cases. In the fetal period, we observed SATB2+ cells in layers II-IV, CUTL1+ cells in layers II-V, FOXP1+ cells in layer V, OTX1+ cells in layers II or V, and CTIP2+ and TBR1+ cells in layers V and VI. SATB2+ and CUTL1+ cells appeared until 3 months of age, but the other markers disappeared after birth. Neocortices of MDS and XLAG infants revealed SATB2+, CUTL1+, FOXP1+, and TBR1+ cells diffusely located in the upper layers. In fetal FCMD neocortex, neurons labeled with the layer-specific markers located over the glia limitans. The present study provided new knowledge indicating that the expression pattern of these markers in the developing human neocortex was similar to those in mice. Various lissencephalies revealed abnormal layer formation by random migration.