埃里克·奥尔森博士

研究抽象

Our laboratory seeks to understand the fundamental mechanisms underlying the migration and dendrite initiation in the developing mammalian cortex.

The mature cortical neuron receives synaptic input via the apical dendrite and integrates this input prior to firing an action potential. 意料之中的是, disruption of dendritic growth and function underlie many neurological disorders including intellectual disability, 癫痫和自闭症.

顶端树突的个体发生: Using multiphoton microscopy we have recently documented that the apical dendrite emerges by direct transformation of the leading process of the migrating neuron. This transformation occurs at the end of the migration route as the leading process contacts the marginal zone of the developing cortex. 在这约2小时的转变过程中，先导过程增长2.5倍的大小，增加分支.5倍(O'Dell et al .., 2015). Branches in the leading process impede migration and therefore a stable branch point may constitute the "stop signal" for neuronal migration. This would suggest that neurons migrate until they encounter dendritic growth cues.

神经元对分泌的糖蛋白Reelin有何反应? Using this multiphoton approach we have examined a mouse model of intellectual disability called the 卷取机 一种叫做Reln (Reelin)的基因突变的老鼠. Reelin is a glycoprotein protein secreted by CR neurons in the region of dendritic initiation and growth. Reelin缺席, 树突丝状伪足从边缘区收缩, the 细胞s became dysmorphic and the dendrites were tangentially oriented. Injection of Reelin protein was able to rescue this dysmorphology and the dendrites became radially oriented with a pial-directed apical dendrite. (更多信息见Nichols et al., 2010; O'Dell et al., 2012; O'Dell et al., 2015).

目前在实验室解决的问题:

What are the other extra细胞ular cues regulating dendritic polarized dendritic growth? Reelin is likely a permissive signal and works in conjunction with multiple other signaling pathways to mediate its biological effect. We are identifying other cues that cooperate with Reelin to mediate this stabilization and polarization of the apical dendrite.

乙醇暴露会破坏reelin信号传导吗? As part of an NIAAA funded center (DEARC) we are examining the possibility that ethanol exposure disrupts dendritic growth and Reelin-signaling during development. This disruption could contribute to the intellectual disability observed with Fetal 酒精 Syndrome (FAS). (更多信息见Powrozek et al., 2012; Olson, 2014).

树突起始过程中基因表达的控制: 在之前的一项研究中(Cameron等人)., 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. At least half of the validated 3-fold up genes have been associated with neurological disease including autism and intellectual disability. This finding underscores not only the extreme dynamism of dendritogenic period, involving the cessation of migration and the elaboration of both dendrites and axons, 但也可能与神经系统疾病有关. What triggers this increase in gene expression at the end of the migration route?

焦点粘附适配器: 与博士合作. 克里斯·特纳(纽约州立大学上州分校), we have generated conditional knockout mice for the focal adhesion adaptor proteins Paxillin and Hic5 and are examining their role in cortical neuron migration and dendritogenesis.

选定的出版物

Rashid M, Belmont J, Carpenter D, Turner CE， 奥尔森EC. Neural-specific deletion of the focal adhesion adaptor protein paxillin slows migration speed and delays cortical layer formation. 发展. 2017年11月1日;144(21):4002-4014. doi: 10.1242 / dev.147934. Epub 2017 9月21日.PMID: 28935710

Lammert DB, Middleton FA, Pan J， 奥尔森ECHowell BW.The de novo autism spectrum disorder RELN R2290C mutation reduces Reelin secretion and increases protein disulfide isomerase expression. J Neurochem. 2017年7月,142 (1):89 - 102. doi: 10.1111 / jnc.14045. 2017年5月18日. PMID: 28419454

Goreczny GJ, Ouderkirk-Pecone JL， 奥尔森EC，克伦德尔M，特纳CE. Hic-5 remodeling of the stromal matrix promotes breast tumor progression. 致癌基因. 2017年05月11日;36(19):2693-2703. doi: 10.1038 / onc.2016.422. Epub 2016年11月28日.PMID: 27893716

O'Dell RS, Cameron DA, Zipfel WR， 奥尔森EC. Reelin Prevents Apical Neurite Retraction during Terminal Translocation and Dendrite Initiation. J >. 2015年7月29日;35(30):10659-74. doi: 10.1523 / JNEUROSCI.1629-15.2015.PMID:26224852(封面文章).

奥尔森EC. Analysis of preplate splitting and early cortical development illuminates the biology of neurological disease. 前面Pediatr. 2014年11月11日;2:21 1. doi: 10.3389 / fp.2014.00121. eCollection 2014. 审查.PMID: 25426475

Dixit R, Wilkinson G, Cancino GI, Shaker T, Adnani L, Li S, Dennis D, Kurrasch D, Chan JA, 奥尔森EC， Kaplan DR, Zimmer C, Schuurmans C. Neurog1 and Neurog2 control two waves of neuronal differentiation in the piriform cortex. J >. 2014年1月8日;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， 奥尔森EC， Kessler JA陈安. Cadherin-11 regulates motility in normal cortical neural precursors and glioblastoma. 《推荐最近最火的赌博软件》. 2013 Aug 7;8(8):e70962. doi: 10.1371 /杂志.玉米饼.0070962. eCollection 2013.PMID: 23951053

尼科尔斯AJ, O'Dell RS, Powrozek TA， 奥尔森EC. Ex utero electroporation and whole hemisphere explants: a simple experimental method for studies of early cortical development. J Vis Exp. 2013年4月3日;. doi: 10.3791/50271.PMID: 23609059

Powrozek助教, 奥尔森EC. 乙醇诱导的高尔基体形态破坏, primary neurite number and 细胞ular orientation in developing cortical neurons. 酒精. 2012年11月,46(7):619 - 27所示. doi: 10.1016/j.酒精.2012.07.003. 2012年7月25日.PMID: 22840816

O'Dell RS, Ustine CJ, Cameron DA, Lawless SM, Williams RM, Zipfel WR, 奥尔森EC. Layer 6 cortical neurons require Reelin-Dab1 signaling for 细胞ular orientation, 高尔基部署, 并引导神经突起生长到边缘区域. 神经系统开发. 2012年7月7日;7:25. doi: 10.1186/1749-8104-7-25.PMID: 22770513 (高访问)

Cameron DA, Middleton FA, chen A， 奥尔森EC. Hierarchical clustering of gene expression patterns in the Eomes + lineage of excitatory neurons during early neocortical development. BMC >. 2012年8月1日;13:90. doi: 10.1186/1471-2202-13-90.PMID: 22852769 (高访问)

Matsuki T, Matthews RT, Cooper JA, van der Brug MP, Cookson MR, Hardy JA, 奥尔森ECHowell BW. Reelin and stk25 have opposing roles in neuronal polarization and dendritic 高尔基部署. 细胞. 2010年11月24日;143(5):826-36. doi: 10.1016/j.细胞.2010.10.029.PMID: 21111240

Mutch CA, Schulte JD， 奥尔森E陈安. Beta-catenin signaling negatively regulates intermediate progenitor population numbers in the developing cortex. 《推荐最近最火的赌博软件》. 2010年8月25日;5(8):e12376. doi: 10.1371 /杂志.玉米饼.0012376.PMID: 20811503

尼科尔斯AJ, 奥尔森EC. Reelin promotes neuronal orientation and dendritogenesis during preplate splitting. Cereb皮层. 2010年9月,20(9):2213 - 23所示. doi: 10.1093 / cercor / bhp303. Epub 2010年1月11日.PMID: 20064940