A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.
A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.
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DOI：
10.1016/j.neuron.2011.11.036
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发表时间：
2012-02-23
期刊：
影响因子：
16.2
通讯作者：
Pleasure SJ
中科院分区：
文献类型：
--
作者：
Choe Y;Siegenthaler JA;Pleasure SJ
胼胝体是大脑皮质两半球之间最重要的连合连接，许多神经发育障碍与胼胝体发育不全有关。使用脑膜过度生长或脑膜选择性缺失的小鼠，我们已经确定了一系列由脑膜启动的调节胼胝体发育的形态发生信号。脑膜产生BMP 7，一种胼胝体轴突生长的抑制剂。通过胼胝体寻路神经元诱导Wnt 3的表达来克服这种活性，所述Wnt 3的表达拮抗BMP 7的抑制作用。Wnt 3在扣带回胼胝体寻路轴突中的表达受到另一个BMP家族成员GDF 5的发育调节，GDF 5由相邻的Cajal-Retzius神经元产生，并在胼胝体轴突长出之前开启。GDF 5的作用反过来又受脑膜产生的可溶性GDF 5抑制剂Dan的控制。因此，脑膜和内侧新皮层使用级联信号来调节胼胝体发育。
The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. Using mice with either meningeal overgrowth or selective loss of meninges, we’ve identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonizes the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development.
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