Bach Antoine, Lallemand Yvan, Nicola Marie-Anne, Ramos Casto, Mathis Luc, Maufras Mathilde, Robert Benoît
Unité de Génétique Moléculaire de la Morphogenèse, Institut Pasteur, URA 2578 du CNRS, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Development. 2003 Sep;130(17):4025-36. doi: 10.1242/dev.00609.
The dorsal midline of the neural tube has recently emerged as a major signaling center for dorsoventral patterning. Msx genes are expressed at the dorsal midline, although their function at this site remains unknown. Using Msx1(nlacZ) mutant mice, we show that the normal expression domain of Msx1 is interrupted in the pretectum of mutant embryos. Morphological and gene expression data further indicate that a functional midline is not maintained along the whole prosomere 1 in Msx1 mutant mice. This results in the downregulation of genes expressed laterally to the midline in prosomere 1, confirming the importance of the midline as a signaling center. Wnt1 is essential for dorsoventral patterning of the neural tube. In the Msx1 mutant, Wnt1 is downregulated before the midline disappears, suggesting that its expression depends on Msx1. Furthermore, electroporation in the chick embryo demonstrates that Msx1 can induce Wnt1 expression in the diencephalon neuroepithelium and in the lateral ectoderm. In double Msx1/Msx2 mutants, Wnt1 expression is completely abolished at the dorsal midline of the diencephalon and rostral mesencephalon. This indicates that Msx genes may regulate Wnt1 expression at the dorsal midline of the neural tube. Based on these results, we propose a model in which Msx genes are intermediary between Bmp and Wnt at this site.
神经管的背中线最近已成为背腹模式形成的主要信号中心。Msx基因在背中线表达，尽管它们在该位点的功能尚不清楚。利用Msx1(nlacZ)突变小鼠，我们发现Msx1的正常表达域在突变胚胎的顶盖前区被中断。形态学和基因表达数据进一步表明，Msx1突变小鼠的整个前脑原节1中功能性中线无法维持。这导致前脑原节1中线外侧表达的基因下调，证实了中线作为信号中心的重要性。Wnt1对神经管的背腹模式形成至关重要。在Msx1突变体中，Wnt1在中线消失之前就被下调，表明其表达依赖于Msx1。此外，在鸡胚中的电穿孔实验表明，Msx1可诱导间脑神经上皮和外侧外胚层中Wnt1的表达。在Msx1/Msx2双突变体中，间脑和中脑前部背中线处的Wnt1表达完全消失。这表明Msx基因可能在神经管背中线调节Wnt1的表达。基于这些结果，我们提出了一个模型，其中Msx基因在此位点是Bmp和Wnt之间的中介。
