Boekhoorn Karin, Sarabdjitsingh Angela, Kommerie Hendrik, de Punder Karin, Schouten Theo, Lucassen Paul J, Vreugdenhil Erno
Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands.
J Comp Neurol. 2008 Apr 1;507(4):1639-52. doi: 10.1002/cne.21646.
During corticogenesis, radial glia-derived neural progenitors divide and migrate along radial fibers to their designated positions within the cortical plate. The microtubule-associated proteins doublecortin (DCX) and doublecortin-like (DCL) are critically involved in neuronal migration and division, and may function in a partially redundant pathway. Since little is known about the important early stages of corticogenesis, when neurogenesis is extensive, we addressed a possible differential role by examining spatiotemporal expression patterns of DCX, DCL, and the radial glia marker vimentin during murine development. We found expression patterns of DCL and DCX to differ remarkably prior to embryonic day (E)13. DCL was already expressed at E9 and largely overlapped with vimentin, whereas DCX expression started modestly from E10/E11 onward. DCL was mainly found in the ventricular zone, often in mitotic cells and in pial-oriented radial fibers. In contrast, DCX was expressed in tangential fibers in the outer cortical regions. After E13, DCX and DCL expression largely overlapped but DCL expression had disappeared from the ventricular zone. Also, DCL levels were attenuated, whereas DCX remained high beyond E17. In conclusion, DCX and DCL are differentially expressed, particularly during early corticogenesis, consistent with their different functional roles. Given its involvement in mitosis, DCL appears to have a unique role in the early neuroepithelium that is different from later developmental stages when DCX is coexpressed.
在皮质发生过程中,源自放射状胶质细胞的神经祖细胞沿着放射状纤维分裂并迁移至皮质板内的指定位置。微管相关蛋白双皮质素(DCX)和双皮质素样蛋白(DCL)在神经元迁移和分裂中起关键作用,且可能在部分冗余途径中发挥功能。由于在神经发生广泛的皮质发生早期重要阶段所知甚少,我们通过检测DCX、DCL和放射状胶质细胞标志物波形蛋白在小鼠发育过程中的时空表达模式,探讨了它们可能存在的不同作用。我们发现,在胚胎第(E)13天之前,DCL和DCX的表达模式有显著差异。DCL在E9时就已表达,且与波形蛋白大量重叠,而DCX的表达从E10/E11开始适度增加。DCL主要存在于脑室区,常见于有丝分裂细胞和朝向软脑膜的放射状纤维中。相比之下,DCX在外皮质区域的切线纤维中表达。E13之后,DCX和DCL的表达大量重叠,但DCL的表达已从脑室区消失。此外,DCL水平降低,而DCX在E17之后仍保持高表达。总之,DCX和DCL存在差异表达,尤其是在皮质发生早期,这与其不同的功能作用一致。鉴于DCL参与有丝分裂,它似乎在早期神经上皮中具有独特作用,这与DCX共表达的后期发育阶段不同。