Gulacsi Alexandra A, Anderson Stewart A
Department of Psychiatry, Weill Medical College of Cornell University, 1300 York Avenue, Box 244, New York, New York, 10065, USA.
Nat Neurosci. 2008 Dec;11(12):1383-91. doi: 10.1038/nn.2226. Epub 2008 Nov 9.
Development of the telencephalon involves the coordinated growth of diversely patterned brain structures. Previous studies have demonstrated the importance of beta-catenin-mediated Wnt signaling in proliferation and fate determination during cerebral cortical development. We found that beta-catenin-mediated Wnt signaling critically maintained progenitor proliferation in the subcortical (pallidal) telencephalon. Targeted deletion of beta-catenin in mice severely impaired proliferation in the medial ganglionic eminence without grossly altering differentiated fate. Several lines of evidence suggest that this phenotype is primarily the result of a loss of canonical Wnt signaling. As previous studies have suggested that the ventral patterning factor Sonic Hedgehog (Shh) also stimulates dorsal telencephalic proliferation, we propose a model whereby Wnt and Shh signaling promote distinct dorsal-ventral patterning while also having broader effects on proliferation that serve to coordinate the growth of telencephalic subregions.
端脑的发育涉及多种模式化脑结构的协调生长。先前的研究已经证明β-连环蛋白介导的Wnt信号在大脑皮质发育过程中的增殖和命运决定中具有重要作用。我们发现β-连环蛋白介导的Wnt信号对于维持皮质下（苍白球）端脑祖细胞的增殖至关重要。在小鼠中靶向缺失β-连环蛋白会严重损害内侧神经节隆起的增殖，而不会显著改变分化命运。多项证据表明，这种表型主要是经典Wnt信号缺失的结果。由于先前的研究表明腹侧模式形成因子音猬因子（Shh）也能刺激背侧端脑的增殖，我们提出了一个模型，即Wnt和Shh信号促进不同的背腹模式形成，同时对增殖具有更广泛的影响，从而协调端脑子区域的生长。
