当前位置: X-MOL 学术bioRxiv. Dev. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The transcription factor BCL11A defines a distinctive subset of dopamine neurons in the developing and adult midbrain
bioRxiv - Developmental Biology Pub Date : 2020-10-07 , DOI: 10.1101/2020.10.06.327940
Marianna Tolve , Ayse Ulusoy , Khondker Ushna Sameen Islam , Gabriela O. Bodea , Ece Öztürk , Bianca Broske , Astrid Mentani , Antonia Wagener , Karen van Loo , Stefan Britsch , Pengtao Liu , Walid Khaled , Stephan Baader , Donato A. Di Monte , Sandra Blaess

Midbrain dopaminergic (mDA) neurons are diverse in their projection targets, impact on behavior and susceptibility to neurodegeneration. Little is known about the molecular mechanisms that establish this diversity in mDA neurons during development. We find that the transcription factor Bcl11a defines a subset of mDA neurons in the developing and adult murine brain. By combining intersectional labeling and viral-mediated tracing we show that Bcl11a-expressing mDA neurons form a highly specific subcircuit within the dopaminergic system. We demonstrate that Bcl11a-expressing mDA neurons in the substantia nigra (SN) are particularly vulnerable to neurodegeneration in an a-synuclein overexpression model of Parkinson's disease. Inactivation of Bcl11a in developing mDA neurons results in anatomical changes, deficits in motor learning and a dramatic increase in the susceptibility to a-synucleininduced degeneration in SN-mDA neurons. In summary, we identify an mDA subpopulation with highly distinctive characteristics defined by the expression of the transcription factor Bcl11a already during development.

中文翻译:

转录因子BCL11A定义了发育中和成年中脑中多巴胺神经元的独特子集

中脑多巴胺能神经元(mDA)的投射目标,对行为的影响和对神经退行性的敏感性各不相同。关于在发育过程中建立mDA神经元多样性的分子机制知之甚少。我们发现,转录因子Bcl11a定义了发育中和成年鼠脑中mDA神经元的一个子集。通过结合交叉标记和病毒介导的示踪,我们表明表达Bcl11a的mDA神经元在多巴胺能系统内形成高度特异性的子回路。我们证明黑质(SN)中表达Bcl11a的mDA神经元特别容易在帕金森氏病的α-突触核蛋白过表达模型中发生神经变性。发育中的mDA神经元中Bcl11a的失活导致解剖学改变,运动学习障碍和SN-mDA神经元对α-突触核蛋白引起的变性的敏感性显着增加。总之,我们确定了在发育过程中已经具有转录因子Bcl11a表达的mDA亚群。
更新日期:2020-10-08
down
wechat
bug