Abnormal positioning of diencephalic cell types in neocortical tissue in the dorsal telencephalon of mice lacking functional Gli3.
Abnormal positioning of diencephalic cell types in neocortical tissue in the dorsal telencephalon of mice lacking functional Gli3.
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DOI：
10.1523/jneurosci.2673-06.2006
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发表时间：
2006-09-06
影响因子：
5.3
通讯作者：
Price, David J
中科院分区：
文献类型：
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作者：
Fotaki, Vassiliki;Yu, Tian;Zaki, Paulette A;Mason, John O;Price, David J
转录因子Gli3（胶质瘤相关癌基因同源物）对哺乳动物前脑的正常发育至关重要。Gli3的一个极端需求是在背内侧端脑，在缺乏功能性Gli3的Gli3Xt/Xt突变小鼠中不形成。在这项研究中，我们分析了Gli3在野生型端脑中的表达，并观察到Gli3蛋白的高背侧到低腹侧的表达梯度和背侧裂解形式的优势。这种分级表达与Gli3Xt/Xt小鼠中观察到的轻度至轻度腹侧端脑表型相关。我们描述了Gli3Xt/Xt小鼠在皮质发生早期的端脑与间脑的异常连接，并确定了背端脑的内侧界限。基于这一分析，我们得出结论，之前被描述为在背端脑的腹侧端脑标记的一些异常表达实际上是在邻近的间脑组织中表达的，后者表达了许多标记腹侧端脑的相同基因。我们观察到，在胚胎第10.5天，即前脑泡解剖细分一天后，表达Gli3Xt/Xt端脑的Foxg1（叉头盒）中偶有间脑特征的细胞。在较晚的年龄，当新皮层变得高度混乱，形成主要由神经祖细胞组成的玫瑰花丛时，大群这样的细胞出现在Gli3Xt/Xt新皮层区域。我们认为Gli3对于形成完整的端脑-间脑边界和防止间脑细胞在端脑背侧的异常定位是必不可少的。
The transcription factor Gli3 (glioma-associated oncogene homolog) is essential for normal development of the mammalian forebrain. One extreme requirement for Gli3 is at the dorsomedial telencephalon, which does not form in Gli3Xt/Xt mutant mice lacking functional Gli3. In this study, we analyzed expression of Gli3 in the wild-type telencephalon and observed a highdorsal-to-lowventral gradient of Gli3 expression and predominance of the cleaved form of the Gli3 protein dorsally. This graded expression correlates with the severedorsal-to-mildventral telencephalic phenotype observed in Gli3Xt/Xt mice. We characterized the abnormal joining of the telencephalon to the diencephalon and defined the medial limit of the dorsal telencephalon in Gli3Xt/Xt mice early in corticogenesis. Based on this analysis, we concluded that some of the abnormal expression of ventral telencephalic markers previously described as being in the dorsal telencephalon is, in fact, expression in adjacent diencephalic tissue, which expresses many of the same genes that mark the ventral telencephalon. We observed occasional cells with diencephalic character in the Foxg1 (forkhead box)-expressing Gli3Xt/Xt telencephalon at embryonic day 10.5, a day after the anatomical subdivision of the forebrain vesicle. Large clusters of such cells appear in the Gli3Xt/Xt neocortical region at later ages, when the neocortex becomes highly disorganized, forming rosettes comprising mainly neural progenitors. We propose that Gli3 is indispensable for formation of an intact telencephalic-diencephalic boundary and for preventing the abnormal positioning of diencephalic cells in the dorsal telencephalon.