Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding
Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding
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DOI：
10.1002/cne.10550
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发表时间：
2003-03-17
影响因子：
2.5
通讯作者：
O'Leary, DDM
中科院分区：
文献类型：
--
作者：
Bishop, KM;Garel, S;O'Leary, DDM
同源框转录因子Emx 1和Emx 2以重叠模式表达，包括端脑背侧神经上皮中的皮质祖细胞。我们已经解决了合作的Emx 1和Emx 2在皮质发育的Emx 1，Emx 2双突变小鼠与野生型和Emx 1和Emx 2单突变体的表型比较。与野生型和EMX单突变体相比，EMX双突变体的皮质大大减少;海马和齿状回缺失，嗅球的生长和分层缺陷。细胞增殖和死亡在皮质神经发生的早期是相对正常的，这表明双突变皮质发育不全主要是由于早期的图案缺陷。皮质标记物的表达在减少的双突变体新皮质中持续存在，但表现出的层状模式不如正常的尖锐，与缺陷的细胞结构一致，可能部分是由于前板和Reelin阳性Cajal-Retzius神经元的数量减少。亚板神经元在双突变体中也表现出异常分化。皮质传出轴突不能离开双突变皮质，TCA穿过纹状体并接近皮质但不进入它，这种TCA寻路缺陷似乎是非细胞自主的，并支持皮质传出轴突是引导TCA进入皮质所需的支架的假设。在双突变体中，一些TCAs未能变成腹侧端脑，并采取异常的腹侧轨迹;这种寻路缺陷与腹侧端脑中的Emx 2表达结构域相关。在Emx双突变体更严重的表型表明，Emx 1和Emx 2合作，以调节皮质发育的多个功能。
The homeobox transcription factors Emx1 and Emx2 are expressed in overlapping patterns that include cortical progenitors in the dorsal telencephalic neuroepithelium. We have addressed cooperation of Emx1 and Emx2 in cortical development by comparing phenotypes in Emx1; Emx2 double mutant mice with wild-type and Emx1 and Emx2 single mutants. Emx double mutant cortex is greatly reduced compared with wild types and Emx single mutants; the hippocampus and dentate gyrus are absent, and growth and lamination of the olfactory bulbs are defective. Cell proliferation and death are relatively normal early in cortical neurogenesis, suggesting that hypoplasia of the double mutant cortex is primarily due to earlier patterning defects. Expression of cortical markers persists in the reduced double mutant neocortex, but the laminar patterns exhibited are less sharp than normal, consistent with deficient cytoarchitecture, probably due in part to reduced numbers of preplate and Reelin-positive Cajal-Retzius neurons. Subplate neurons also exhibit abnormal differentiation in double mutants. Cortical efferent axons fail to exit the double mutant cortex, and TCAs pass through the striatum and approach the cortex but do not enter it. This TCA pathfinding defect appears to be non-cell autonomous and supports the hypothesis that cortical efferents are required scaffolds to guide TCAs into cortex. In double mutants, some TCAs fail to turn into ventral telencephalon and take an aberrant ventral trajectory; this pathfinding defect correlates with an Emx2 expression domain in ventral telencephalon. The more severe phenotypes in Emx double mutants suggest that Emx1 and Emx2 cooperate to regulate multiple features of cortical development.