Deregulated Rac1 Activity in Neural Crest Controls Cell Proliferation, Migration and Differentiation During Midbrain Development.
Deregulated Rac1 Activity in Neural Crest Controls Cell Proliferation, Migration and Differentiation During Midbrain Development.
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DOI：
10.3389/fcell.2021.704769
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发表时间：
2021
影响因子：
5.5
通讯作者：
He F
中科院分区：
文献类型：
--
作者：
Gahankari A;Dong C;Bartoletti G;Galazo M;He F
RAC1等位基因突变与多发性脑肿瘤有关，表明严格控制RAC1活性对于神经组织的正常发育和动态平衡是必要的。为了了解升高的rac1活性如何影响神经脊细胞(NCCs)的发育，我们产生了rac1CA；WNT1-Cre2小鼠，在其中，一个结构性活性的rac1G12V突变体在NCCs的衍生品中特异性地表达。我们的结果显示，增强的rac1活性导致中脑增大和细胞密度改变，伴随着NCCs增殖率的增加和细胞的错误迁移。有趣的是，我们的实验数据还显示，NCCs中rac1活性的升高扰乱了腹侧中脑中多巴胺能神经元前体的区域化，并损害了它们的分化。这些发现从细胞和分子水平上阐明了RAC1突变与脑肿瘤相关的机制。
Mutations in RAC1 allele are implicated in multiple brain tumors, indicating a rigorous control of Rac1 activity is required for neural tissue normal development and homeostasis. To understand how elevated Rac1 activity affects neural crest cells (NCCs) development, we have generated Rac1CA;Wnt1-Cre2 mice, in which a constitutively active Rac1G12V mutant is expressed specifically in NCCs derivatives. Our results revealed that augmented Rac1 activity leads to enlarged midbrain and altered cell density, accompanied by increased NCCs proliferation rate and misrouted cell migration. Interestingly, our experimental data also showed that elevated Rac1 activity in NCCs disrupts regionalization of dopaminergic neuron progenitors in the ventral midbrain and impairs their differentiation. These findings shed light on the mechanisms of RAC1 mutation correlated brain tumor at the cellular and molecular level.
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影响因子：
5.3
作者：
Cajanek, Lukas;Ganji, Ranjani Sri;Arenas, Ernest
通讯作者：
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影响因子：
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通讯作者：
Arenas E