Role of Non-catalytic form of TrkC receptor in cell fate specification of neocortical progenitors

TrkC 受体非催化形式在新皮质祖细胞命运规范中的作用

• 批准号: 299061699
• 负责人: Professor Dr. Victor Tarabykin
• 金额: --
• 依托单位: Institut für Zell- und Neurobiologie (CCM)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/299061699?language=en
• 关键词: Role; Non; catalytic; form; TrkC

Neocortical progenitors successively give rise to a heterogeneous population of neurons during development so that early progenitors generate deep layer neurons while late progenitors generate upper layer neurons. Understanding how this process is regulated is vital for understanding crucial aspects of neocortical evolution and ultimately development of the human neocortex. The program of corticogenesis has been shown to be intrinsically hard-wired within cortical progenitors, however molecular mechanisms that control the different potentials of early and late progenitors are not known. Recently, we discovered that the expression of TrkC T1, a splice variant of the neurotrophin receptor TrkC that lacks the intracellular kinase domain (non-catalytic TrkC), distinguishes early from late neocortical progenitors. In progenitor cells, TrkC T1 is expressed within a short temporal window that coincides with deeper layer neurogenesis and is down-regulated during upper layer neurogenesis. In vivo, down regulation of TrkC T1 expression in neocortical progenitors induces a reduction in the number of deep layer neurons while upregulation of TrkC T1 expression induces an increase in the number of deeper layer at the expense of upper layers neurons. In the current project proposal, we intend to identify the molecular mechanisms that act downstream of non-catalytic TrkC to control cell fate decisions in the developing neocortex.

新皮质祖细胞在发育过程中连续产生异质性神经元群体，使得早期祖细胞产生深层神经元，而晚期祖细胞产生上层神经元。了解这一过程是如何调节的，对于理解新皮层进化的关键方面以及人类新皮层的最终发展至关重要。皮质发生的程序已被证明是内在的硬连线内的皮质祖细胞，然而，控制早期和晚期祖细胞的不同潜力的分子机制是未知的。最近，我们发现，表达的TrkC T1，剪接变体的神经营养因子受体TrkC，缺乏细胞内激酶结构域（非催化TrkC），区分早期和晚期新皮质祖细胞。在祖细胞中，TrkC T1在与更深层神经发生一致的短时间窗内表达，并且在上层神经发生期间下调。在体内，下调TrkC T1在新皮层祖细胞中的表达诱导深层神经元数目的减少，而上调TrkC T1表达诱导以上层神经元为代价的深层神经元数目的增加。在目前的项目提案中，我们打算确定在发育中的新皮层中作用于非催化TrkC下游以控制细胞命运决定的分子机制。

项目成果

TrkC-T1, the Non-Catalytic Isoform of TrkC, Governs Neocortical Progenitor Fate Specification by Inhibition of MAP Kinase Signaling.

TrkC-T1 是 TrkC 的非催化亚型，通过抑制 MAP 激酶信号传导来控制新皮质祖细胞的命运规范

• DOI: 10.1093/cercor/bhab172
• 发表时间: 2021
• 期刊: Cerebral cortex
• 影响因子: 3.7
• 作者: Parthasarathy S;Srivatsa S;Weber AI;Graber N;Britanova OV;Borisova E;Bessa P;Ambrozkiewicz MC;Rosario M;Tarabykin V
• 通讯作者: Tarabykin V

Ablation of Vti1a/1b Triggers Neural Progenitor Pool Depletion and Cortical Layer 5 Malformation in Late-embryonic Mouse Cortex

• DOI: 10.1016/j.neuroscience.2021.03.021
• 发表时间: 2021-03
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: G. Sokpor;Joachim Rosenbusch;A. Kunwar;M. Rickmann;Tran Tuoc;S. Rizzoli;V. Tarabykin;G. F. V. Mollard;K. Krieglstein;J. Staiger

Srsf10 and the minor spliceosome control tissue-specific and dynamic SR protein expression

• DOI: 10.7554/elife.56075
• 发表时间: 2020-04-27
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Meinke, Stefan;Goldammer, Gesine;Heyd, Florian
• 通讯作者: Heyd, Florian