Monuki E S, Porter F D, Walsh C A
Division of Neurogenetics, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Neuron. 2001 Nov 20;32(4):591-604. doi: 10.1016/s0896-6273(01)00504-9.
The organizing centers and molecules that pattern the cerebral cortex have been elusive. Here we show that cortical patterning involves regulation of the Lhx2 homeobox gene by the roof plate. Roof plate ablation results in reduced cortical size and Lhx2 expression defects that implicate roof plate signals in the bimodal regulation of Lhx2 in vivo. Bimodal Lhx2 regulation can be recapitulated in explants using two roof plate-derived signaling molecules, Bmp4 and Bmp2. Loss of Lhx2 function results in profound losses of cortical progenitors and neurons, but Lhx2 mutants continue to generate cortical neurons from dorsal sources that may include the roof plate region itself. These findings provide evidence for the roof plate as an organizing center of the developing cortex and for a roof plate-Lhx2 pathway in cortical patterning.
构建大脑皮层结构的组织中心和分子一直难以捉摸。在此我们表明，皮层结构的形成涉及顶板对Lhx2同源框基因的调控。顶板切除导致皮层尺寸减小以及Lhx2表达缺陷，这表明顶板信号在体内对Lhx2进行双峰调节。使用两种源自顶板的信号分子Bmp4和Bmp2，可在外植体中重现Lhx2的双峰调节。Lhx2功能缺失导致皮层祖细胞和神经元大量减少，但Lhx2突变体仍能从包括顶板区域本身在内的背侧来源继续产生皮层神经元。这些发现为顶板作为发育中皮层的组织中心以及皮层结构形成中的顶板-Lhx2通路提供了证据。
