Eric Olson, PhD

RESEARCH ABSTRACT

我们的实验室旨在了解哺乳动物皮层迁移和树突起始的基本机制.

成熟的皮层神经元通过顶树突接收突触输入，并在动作电位放电前整合这些输入. Unsurprisingly, 树突生长和功能的破坏是包括智力残疾在内的许多神经系统疾病的基础, epilepsy and autism.

Ontogeny of the apical dendrite: 利用多光子显微镜，我们最近记录了顶端树突是由迁移神经元的先导过程直接转化而产生的. 这种转变发生在迁移路线的末端，因为领先的过程与发育中的皮层的边缘区域接触. During this ~2 hr transformation, the leading process grows 2.5 fold in size and increases its branching 3.5 fold (O'Dell et al., 2015). 超前过程中的分支阻碍迁移，因此一个稳定的分支点可能构成神经元迁移的“停止信号”. 这表明神经元会迁移，直到它们遇到树突生长的信号.

How do neurons respond to the secreted glycoprotein Reelin? 利用这种多光子方法，我们研究了一种智力残疾的老鼠模型 reeler mouse that has a mutation in a gene called Reln (Reelin). Reelin是CR神经元在树突起始和生长区域分泌的一种糖蛋白. Absent Reelin, the dendritic filopodia retracted away from the marginal zone, 细胞变形，树突切向. 注射Reelin蛋白可以恢复这种畸形，树突向径向定向，形成一个尖树突. (For more information see Nichols et al., 2010; O'Dell et al., 2012; O'Dell et al., 2015).

Questions presently addressed in the laboratory:

还有什么细胞外信号调节树突极化生长? Reelin可能是一种允许信号，并与多种其他信号通路一起调节其生物学效应. 我们正在寻找与Reelin合作的其他线索，以介导顶端树突的稳定和极化.

Does ethanol exposure disrupt Reelin-signaling? 作为NIAAA资助中心(DEARC)的一部分，我们正在研究乙醇暴露在发育过程中破坏树突生长和relin信号传导的可能性. 这种破坏可能导致胎儿酒精综合征(FAS)中观察到的智力残疾。. (For more see Powrozek et al., 2012; Olson, 2014).

Control of gene expression during dendritic initiation: In a prior study (Cameron et al., 2012) we found that >220 genes that were upregulated more than 3-fold during the area encompassing the end of migration and the formation of the dendrite. 至少有一半被证实的3折叠基因与神经系统疾病有关，包括自闭症和智力残疾. 这一发现不仅强调了树突形成时期的极端活力, 包括迁移的停止和树突和轴突的发育, but also the potential relevance to neurological disease. 是什么触发了迁徙路线结束时基因表达的增加?

Focal adhesion adaptors: In collaboration with Dr. Chris Turner (SUNY Upstate), 我们已经产生了局点粘附接头蛋白Paxillin和Hic5的条件敲除小鼠，并正在研究它们在皮层神经元迁移和树突发生中的作用.

Selected Publications

Rashid M, Belmont J, Carpenter D, Turner CE, Olson EC. 局部黏附接头蛋白paxillin的神经特异性缺失减慢了迁移速度并延迟了皮质层的形成. Development. 2017 Nov 1;144(21):4002-4014. doi: 10.1242/dev.147934. Epub 2017 Sep 21.PMID:28935710

Lammert DB, Middleton FA, Pan J, Olson EC, Howell BW.新生自闭症谱系障碍RELN R2290C突变减少Reelin分泌并增加蛋白二硫异构酶表达. J Neurochem. 2017 Jul;142(1):89-102. doi: 10.1111/jnc.14045. Epub 2017 May 18. PMID:28419454

Goreczny GJ, Ouderkirk-Pecone JL, Olson EC, Krendel M, Turner CE. Hic-5基质重塑促进乳腺肿瘤进展. Oncogene. 2017 May 11;36(19):2693-2703. doi: 10.1038/onc.2016.422. Epub 2016 Nov 28.PMID:27893716

O'Dell RS, Cameron DA, Zipfel WR, Olson EC. 在末端易位和树突形成过程中，Reelin阻止顶端神经突缩回. J Neurosci. 2015 Jul 29;35(30):10659-74. doi: 10.1523/JNEUROSCI.1629-15.2015.PMID:26224852 (Cover Article).

Olson EC. 板前分裂和早期皮质发育的分析阐明了神经系统疾病的生物学. Front Pediatr. 2014 Nov 11;2:121. doi: 10.3389/fped.2014.00121. eCollection 2014. Review.PMID:25426475

Dixit R, Wilkinson G, Cancino GI, Shaker T, Adnani L, Li S, Dennis D, Kurrasch D, Chan JA， Olson EC, Kaplan DR, Zimmer C, Schuurmans C. Neurog1和Neurog2控制梨状皮质神经元分化的两个波. J Neurosci. 2014 Jan 8;34(2):539-53. doi: 10.1523/JNEUROSCI.0614-13.2014.PMID:24403153

Schulte JD, Srikanth M, Das S, Zhang J, Lathia JD, Yin L, Rich JN, Olson EC, Kessler JA, Chenn A. 钙粘蛋白-11调节正常皮质神经前体和胶质母细胞瘤的运动. PLoS One. 2013 Aug 7;8(8):e70962. doi: 10.1371/journal.pone.0070962. eCollection 2013.PMID:23951053

Nichols AJ, O'Dell RS, Powrozek TA, Olson EC. 体外电穿孔和全半球外植体:一种研究早期皮质发育的简单实验方法. J Vis Exp. 2013 Apr 3;(74). doi: 10.3791/50271.PMID:23609059

Powrozek TA, Olson EC. Ethanol-induced disruption of Golgi apparatus morphology, 皮层神经元发育中的初级神经突数目和细胞取向. Alcohol. 2012 Nov;46(7):619-27. doi: 10.1016/j.alcohol.2012.07.003. Epub 2012 Jul 25.PMID:22840816

O'Dell RS, Ustine CJ, Cameron DA, Lawless SM, Williams RM, Zipfel WR， Olson EC. 第6层皮质神经元需要Reelin-Dab1信号来决定细胞定向, Golgi deployment, and directed neurite growth into the marginal zone. Neural Dev. 2012 Jul 7;7:25. doi: 10.1186/1749-8104-7-25.PMID:22770513 (Highly Accessed)

Cameron DA, Middleton FA, Chenn A, Olson EC. 早期皮层发育过程中Eomes +兴奋性神经元谱系中基因表达模式的层次聚类. BMC Neurosci. 2012 Aug 1;13:90. doi: 10.1186/1471-2202-13-90.PMID:22852769 (Highly Accessed)

Matsuki T, Matthews RT, Cooper JA, van der Brug MP, Cookson MR, Hardy JA， Olson EC, Howell BW. Reelin和stk25在神经元极化和树突高尔基体部署中具有相反的作用. Cell. 2010 Nov 24;143(5):826-36. doi: 10.1016/j.cell.2010.10.029.PMID:21111240

Mutch CA, Schulte JD, Olson E, Chenn A. β -连环蛋白信号负向调节发育中的皮层中间祖细胞种群数量. PLoS One. 2010 Aug 25;5(8):e12376. doi: 10.1371/journal.pone.0012376.PMID:20811503

Nichols AJ, Olson EC. 在板前分裂过程中，Reelin促进神经元定向和树突发生. Cereb Cortex. 2010 Sep;20(9):2213-23. doi: 10.1093/cercor/bhp303. Epub 2010 Jan 11.PMID:20064940