The cortical hem regulates the size and patterning of neocortex
The cortical hem regulates the size and patterning of neocortex
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DOI：
10.1242/dev.106914
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发表时间：
2014-07-01
期刊：
影响因子：
4.6
通讯作者：
Grove, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Caronia-Brown, Giuliana;Yoshida, Michio;Grove, Elizabeth A.
皮质下摆是背内侧端脑中 Wingless 相关 (WNT) 和骨形态发生蛋白 (BMP) 信号传导的来源，是海马体的胚胎组织者。下摆是否是海马体以外皮质模式的主要调节者尚未被研究。我们检查了基因改造小鼠整个大脑皮层的区域组织，使其没有下摆。表明褶边调节皮质半球的背腹侧模式，新皮质，特别是背内侧新皮质，在后期褶边消融胚胎中尺寸减小，而新皮质腹外侧皮质向背侧扩张。出乎意料的是，下摆消融也扰乱了新皮质头尾轴的区域模式。通过特征基因表达鉴定的头侧新皮质区域扩大，尾侧区域缩小。当成纤维细胞生长因子 (FGF) 8 在头端端脑组织中增加时，会发生类似的转变，但 FGF8 来源在血流消融的大脑中没有变化。相反，我们发现 hem WNT 或 BMP 信号或两者在调节控制新皮质区域大小和位置的转录因子方面与 FGF8 具有相反的作用。当下摆被消融时，必要的平衡就会被扰乱，大脑皮层会被向嘴侧化。我们的研究结果揭示了下摆在皮质发育中的作用比以前认识到的更广泛，并强调两个主要信号中心以对抗性方式相互作用来形成大脑皮层。
The cortical hem, a source of Wingless-related (WNT) and bone morphogenetic protein (BMP) signaling in the dorsomedial telencephalon, is the embryonic organizer for the hippocampus. Whether the hem is a major regulator of cortical patterning outside the hippocampus has not been investigated. We examined regional organization across the entire cerebral cortex in mice genetically engineered to lack the hem. Indicating that the hem regulates dorsoventral patterning in the cortical hemisphere, the neocortex, particularly dorsomedial neocortex, was reduced in size in late-stage hem-ablated embryos, whereas cortex ventrolateral to the neocortex expanded dorsally. Unexpectedly, hem ablation also perturbed regional patterning along the rostrocaudal axis of neocortex. Rostral neocortical domains identified by characteristic gene expression were expanded, and caudal domains diminished. A similar shift occurs when fibroblast growth factor (FGF) 8 is increased at the rostral telencephalic organizer, yet the FGF8 source was unchanged in hem-ablated brains. Rather we found that hem WNT or BMP signals, or both, have opposite effects to those of FGF8 in regulating transcription factors that control the size and position of neocortical areas. When the hem is ablated a necessary balance is perturbed, and cerebral cortex is rostralized. Our findings reveal a much broader role for the hem in cortical development than previously recognized, and emphasize that two major signaling centers interact antagonistically to pattern cerebral cortex.