Minocha Shilpi, Valloton Delphine, Ypsilanti Athena R, Fiumelli Hubert, Allen Elizabeth A, Yanagawa Yuchio, Marin Oscar, Chédotal Alain, Hornung Jean-Pierre, Lebrand Cécile
Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland.
1] INSERM UMR-S968, Institut de la Vision, Paris F-75012, France [2] Sorbonne Université, UPMC University Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012, France [3] CNRS, UMR_7210, Paris F-75012, France.
Nat Commun. 2015 Apr 23;6:6887. doi: 10.1038/ncomms7887.
Guidepost cells present at and surrounding the midline provide guidance cues that orient the growing axons through commissures. Here we show that the transcription factor Nkx2.1 known to control the specification of GABAergic interneurons also regulates the differentiation of astroglia and polydendrocytes within the mouse anterior commissure (AC). Nkx2.1-positive glia were found to originate from three germinal regions of the ventral telencephalon. Nkx2.1-derived glia were observed in and around the AC region by E14.5. Thereafter, a selective cell ablation strategy showed a synergistic role of Nkx2.1-derived cells, both GABAergic interneurons and astroglia, towards the proper formation of the AC. Finally, our results reveal that the Nkx2.1-regulated cells mediate AC axon guidance through the expression of the repellent cue, Slit2. These results bring forth interesting insights about the spatial and temporal origin of midline telencephalic glia, and highlight the importance of neurons and astroglia towards the formation of midline commissures.
位于中线处及周围的路标细胞提供引导线索，使生长中的轴突通过连合部定向。我们在此表明，已知控制GABA能中间神经元特化的转录因子Nkx2.1，也调节小鼠前连合（AC）内星形胶质细胞和多突胶质细胞的分化。发现Nkx2.1阳性胶质细胞起源于腹侧端脑的三个生发区域。到胚胎第14.5天，在AC区域内及周围观察到了源自Nkx2.1的胶质细胞。此后，一种选择性细胞消融策略显示，源自Nkx2.1的细胞（包括GABA能中间神经元和星形胶质细胞）对AC的正常形成具有协同作用。最后，我们的结果表明，Nkx2.1调节的细胞通过表达排斥性信号Slit2介导AC轴突引导。这些结果为端脑中线胶质细胞的时空起源带来了有趣的见解，并突出了神经元和星形胶质细胞对中线连合形成的重要性。
