Bhuiyan Mohammad Iqbal Hossain, Kim Seong Yun, Cho Kyung-Ok
Department of Neurology, University of Pittsburgh, Pittsburgh, USA.
Department of Pharmacology, Department of Biomedicine and Health Sciences, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Acta Neurobiol Exp (Wars). 2018;78(4):297-304.
Lin28 has been shown to promote proliferation of progenitors and survival of neurons during cortical neurogenesis. However, the role of Lin28 in the terminal maturation of neurons remains obscured. In this study, we investigated the developmental impact of Lin28 overexpression on neurite outgrowth. Lin28 expression was upregulated by in utero electroporation at E14.5. Two days later, electroporated cortices were dissociated for culturing primary cortical neurons. We found that Lin28 overexpression, which was confirmed immunocytochemically, led to neurite underdevelopment for all time points during culture. Specifically, Lin28-overexpressing cells displayed significantly fewer primary neurites and a decreased dendritic branching index, compared to GFP-expressing controls. Additionally, Lin28 overexpression in primary cortical neurons induced the expression of high mobility group AT-Hook 2 (HMGA2). Taken together, our study demonstrates that constitutive Lin28 expression disrupts cortical neurogenesis resulting in impaired neurite outgrowth with a concomitant induction of HMGA2.
研究表明，Lin28在皮质神经发生过程中可促进祖细胞增殖和神经元存活。然而，Lin28在神经元终末成熟中的作用仍不清楚。在本研究中，我们研究了Lin28过表达对神经突生长的发育影响。在胚胎第14.5天通过子宫内电穿孔上调Lin28表达。两天后，将电穿孔的皮质解离以培养原代皮质神经元。我们发现，经免疫细胞化学证实的Lin28过表达导致培养期间所有时间点的神经突发育不全。具体而言，与表达绿色荧光蛋白（GFP）的对照相比，过表达Lin28的细胞显示出明显更少的初级神经突和降低的树突分支指数。此外，原代皮质神经元中Lin28过表达诱导了高迁移率族AT钩蛋白2（HMGA2）的表达。综上所述，我们的研究表明，组成性Lin28表达会破坏皮质神经发生，导致神经突生长受损，并伴随HMGA2的诱导。
