Department of Developmental Biology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Dev Biol. 2010 Aug 15;344(2):1026-34. doi: 10.1016/j.ydbio.2010.06.025. Epub 2010 Jul 1.
During development, commissural neurons in the spinal cord project their axons across the ventral midline, floor plate, via multiple interactions among temporally controlled molecular guidance cues and receptors. The transcriptional regulation of commissural axon-associated receptors, however, is not well characterized. Spinal dorsal cells are transfated into commissural neurons by misexpression of Mbh1, a Bar-class homeobox gene. We examined the function of another Bar-class homeobox gene, Mbh2, and how Mbh1 and Mbh2 modulate expression of the receptors, leading to midline crossing of axons. Misexpression of Mbh1 and Mbh2 showed the same effects in the spinal cord. The competence of spinal dorsal cells to become commissural neurons was dependent on the embryonic stage, during which misexpression of the Mbh genes was able to activate guidance receptor genes such as Rig1 and Nrp2. Misexpression of Lhx2, which has been recently shown to be involved in Rig1 expression, activated Rig1 but not Nrp2, and was less effective in generating commissural neurons. Moreover, expression of Lhx2 was activated by and required the Mbh genes. These findings have revealed a transcriptional cascade, in which Lhx2-dependent and -independent pathways leading to expression of guidance receptors branch downstream of the Mbh genes.
在脊髓发育过程中，连合神经元通过跨腹中线、基板的多个相互作用，投射其轴突。然而，连合轴突相关受体的转录调控还没有很好地描述。通过过度表达 Mbh1（一种 Bar 类同源盒基因），将脊髓背侧细胞转化为连合神经元。我们研究了另一个 Bar 类同源盒基因 Mbh2 的功能，以及 Mbh1 和 Mbh2 如何调节受体的表达，从而导致轴突中线穿越。Mbh1 和 Mbh2 的过表达在脊髓中显示出相同的效果。脊髓背侧细胞成为连合神经元的能力取决于胚胎发育阶段，在此期间，Mbh 基因的过表达能够激活导向受体基因，如 Rig1 和 Nrp2。最近已经表明，Lhx2 参与 Rig1 的表达，其过表达激活了 Rig1 而不是 Nrp2，并且生成连合神经元的效果较差。此外，Lhx2 的表达被 Mbh 基因激活并需要其。这些发现揭示了一个转录级联，其中依赖于 Lhx2 和不依赖于 Lhx2 的途径导致导向受体的表达分支于 Mbh 基因的下游。
