Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins.
Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins.
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SOX6表达在具有独特特性和胚胎起源的黑质中区分背和腹侧有偏的多巴胺神经元。
DOI：
10.1016/j.celrep.2021.109975
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发表时间：
2021-11-09
期刊：
影响因子：
8.8
通讯作者：
Awatramani R
中科院分区：
文献类型：
--
作者：
Pereira Luppi M;Azcorra M;Caronia-Brown G;Poulin JF;Gaertner Z;Gatica S;Moreno-Ramos OA;Nouri N;Dubois M;Ma YC;Ramakrishnan C;Fenno L;Kim YS;Deisseroth K;Cicchetti F;Dombeck DA;Awatramani R
帕金森病患者黑质腹侧部多巴胺（DA）神经元变性显著，而背侧部DA神经元相对较少。定义每个SNc层的分子，功能和发育特征对于了解其独特的易感性至关重要。我们证明，Sox6表达区分腹侧和背侧偏置DA神经元群体的SNc。腹侧SNc中的Sox6+群体包括Aldh1a1+子集，并且富含支持脆弱性的基因通路。Sox 6+神经元投射到背侧纹状体，并显示与加速度相关的活性。Sox6−神经元投射到内侧、腹侧和尾侧纹状体，并对奖励做出反应。此外，我们表明，这种成人分裂在发育早期编码。总的来说，我们的工作证明了SNc的双重起源，导致DA神经元群具有不同的分子特征，预测和功能。在这项研究中，佩雷拉Luppi等人通过Sox 6谱系分析完善了中脑多巴胺神经元的景观，从分子，解剖学，功能和发育的角度阐明了背侧和腹侧黑质丘脑腹侧部。
Dopamine (DA) neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson’s disease, while those in the dorsal tier are relatively spared. Defining the molecular, functional, and developmental characteristics of each SNc tier is crucial to understand their distinct susceptibility. We demonstrate that Sox6 expression distinguishes ventrally and dorsally biased DA neuron populations in the SNc. The Sox6+ population in the ventral SNc includes an Aldh1a1+ subset and is enriched in gene pathways that underpin vulnerability. Sox6+ neurons project to the dorsal striatum and show activity correlated with acceleration. Sox6− neurons project to the medial, ventral, and caudal striatum and respond to rewards. Moreover, we show that this adult division is encoded early in development. Overall, our work demonstrates a dual origin of the SNc that results in DA neuron cohorts with distinct molecular profiles, projections, and functions. In this study, Pereira Luppi et al. refine the landscape of midbrain dopamine neurons through Sox6 lineage analysis to shed light on dorsal and ventral substantia nigra pars compacta from molecular, anatomical, functional, and developmental perspectives.
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影响因子：
16.2
作者：
Brignani, Sara;Raj, Divya D. A.;Pasterkamp, R. Jeroen
通讯作者：
Pasterkamp, R. Jeroen
影响因子：
2.5
作者：
FALLON, JH;MOORE, RY
通讯作者：
MOORE, RY
影响因子：
6
作者：
Fiorenzano A;Sozzi E;Parmar M;Storm P
通讯作者：
Storm P
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
5.3
作者：
Evans, Rebekah C.;Zhu, Manhua;Khaliq, Zayd M.
通讯作者：
Khaliq, Zayd M.