Grove E A, Tole S, Limon J, Yip L, Ragsdale C W
Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL, USA.
Development. 1998 Jun;125(12):2315-25. doi: 10.1242/dev.125.12.2315.
In the developing vertebrate CNS, members of the Wnt gene family are characteristically expressed at signaling centers that pattern adjacent parts of the neural tube. To identify candidate signaling centers in the telencephalon, we isolated Wnt gene fragments from cDNA derived from embryonic mouse telencephalon. In situ hybridization experiments demonstrate that one of the isolated Wnt genes, Wnt7a, is broadly expressed in the embryonic telencephalon. By contrast, three others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the medial edge of the telencephalon, defining the hem of the cerebral cortex. The Wnt-rich cortical hem is a transient, neuron-containing, neuroepithelial structure that forms a boundary between the hippocampus and the telencephalic choroid plexus epithelium (CPe) throughout their embryonic development. Indicating a close developmental relationship between the cortical hem and the CPe, Wnt gene expression is upregulated in the cortical hem both before and just as the CPe begins to form, and persists until birth. In addition, although the cortical hem does not show features of differentiated CPe, such as expression of transthyretin mRNA, the CPe and cortical hem are linked by shared expression of members of the Bmp and Msx gene families. In the extra-toesJ (XtJ) mouse mutant, telencephalic CPe fails to develop. We show that Wnt gene expression is deficient at the cortical hem in XtJ/XtJ mice, but that the expression of other telencephalic developmental control genes, including Wnt7a, is maintained. The XtJ mutant carries a deletion in Gli3, a vertebrate homolog of the Drosophila gene cubitus interruptus (ci), which encodes a transcriptional regulator of the Drosophila Wnt gene, wingless. Our observations indicate that Gli3 participates in Wnt gene regulation in the vertebrate telencephalon, and suggest that the loss of telencephalic choroid plexus in XtJ mice is due to defects in the cortical hem that include Wnt gene misregulation.
在发育中的脊椎动物中枢神经系统中，Wnt基因家族成员的典型特征是在信号中心表达，这些信号中心决定神经管相邻部分的发育模式。为了确定端脑中的候选信号中心，我们从胚胎小鼠端脑的cDNA中分离出Wnt基因片段。原位杂交实验表明，分离出的Wnt基因之一Wnt7a在胚胎端脑中广泛表达。相比之下，另外三个基因Wnt3a、5a以及一个新的小鼠Wnt基因Wnt2b仅在端脑的内侧边缘表达，确定了大脑皮质的脑嵴。富含Wnt的皮质脑嵴是一个短暂的、含有神经元的神经上皮结构，在整个胚胎发育过程中形成海马体和端脑脉络丛上皮（CPe）之间的边界。Wnt基因表达在CPe开始形成之前和形成之时在皮质脑嵴中上调，并持续到出生，这表明皮质脑嵴和CPe之间存在密切的发育关系。此外，尽管皮质脑嵴没有显示出分化的CPe的特征，如转甲状腺素蛋白mRNA的表达，但CPe和皮质脑嵴通过Bmp和Msx基因家族成员的共同表达而相连。在extra-toesJ（XtJ）小鼠突变体中，端脑CPe无法发育。我们发现XtJ/XtJ小鼠皮质脑嵴中的Wnt基因表达缺陷，但包括Wnt7a在内的其他端脑发育控制基因的表达得以维持。XtJ突变体在Gli3基因中存在缺失，Gli3是果蝇基因肘脉中断（ci）的脊椎动物同源物，ci编码果蝇Wnt基因无翅的转录调节因子。我们的观察结果表明，Gli3参与脊椎动物端脑中Wnt基因的调控，并表明XtJ小鼠端脑脉络丛的缺失是由于皮质脑嵴中的缺陷，包括Wnt基因调控异常。
