Tiveron Marie-Catherine, Rossel Mireille, Moepps Barbara, Zhang Yong Li, Seidenfaden Ralph, Favor Jack, König Norbert, Cremer Harold
Institut de Biologie du Développement de Marseille Luminy, Centre National de la Recherche Scientifique/Université de Mediterranée, 13288 Marseille, France.
J Neurosci. 2006 Dec 20;26(51):13273-8. doi: 10.1523/JNEUROSCI.4162-06.2006.
Most cortical interneurons are generated in the subpallial ganglionic eminences and migrate tangentially to their final destinations in the neocortex. Within the cortex, interneurons follow mainly stereotype routes in the subventricular zone/intermediate zone (SVZ/IZ) and in the marginal zone. It has been suggested that interactions between invading interneurons and locally generated projection neurons are implicated in the temporal and spatial regulation of the invasion process. However, so far experimental evidence for such interactions is lacking. We show here that the chemokine stromal-derived factor 1 (SDF-1; CXCL12) is expressed in the main invasion route for cortical interneurons in the SVZ/IZ. Most SDF-1-positive cells are proliferating and express the homeodomain transcription factors Cux1 and Cux2. Using MASH-1 mutant mice in concert with the interneuron marker DLX, we exclude that interneurons themselves produce the chemokine in an autocrine manner. We conclude that the SDF-1-expressing cell population represents the precursors of projection neurons during their transition and amplification in the SVZ/IZ. Using mice lacking the SDF-1 receptor CXCR4 or Pax6, we demonstrate that SDF-1 expression in the cortical SVZ/IZ is essential for recognition of this pathway by interneurons. These results represent the first evidence for a molecular interaction between precursors of projection neurons and invading interneurons during corticogenesis.
大多数皮质中间神经元在皮质下神经节隆起处产生，并沿切线方向迁移至新皮质的最终目的地。在皮质内，中间神经元主要沿着脑室下区/中间区（SVZ/IZ）和边缘区的固定路线迁移。有人提出，侵入的中间神经元与局部产生的投射神经元之间的相互作用参与了侵袭过程的时间和空间调节。然而，迄今为止，尚无此类相互作用的实验证据。我们在此表明，趋化因子基质衍生因子1（SDF-1；CXCL12）在SVZ/IZ中皮质中间神经元的主要侵袭路线中表达。大多数SDF-1阳性细胞正在增殖，并表达同源结构域转录因子Cux1和Cux2。使用MASH-1突变小鼠并结合中间神经元标记物DLX，我们排除了中间神经元自身以自分泌方式产生趋化因子的可能性。我们得出结论，表达SDF-1的细胞群体代表了投射神经元在SVZ/IZ中过渡和扩增过程中的前体细胞。使用缺乏SDF-1受体CXCR4或Pax6的小鼠，我们证明皮质SVZ/IZ中SDF-1的表达对于中间神经元识别该途径至关重要。这些结果代表了在皮质发生过程中投射神经元前体细胞与侵入的中间神经元之间分子相互作用的首个证据。
