Martín-Ibáñez Raquel, Pardo Mónica, Giralt Albert, Miguez Andrés, Guardia Inés, Marion-Poll Lucile, Herranz Cristina, Esgleas Miriam, Garcia-Díaz Barriga Gerardo, Edel Michael J, Vicario-Abejón Carlos, Alberch Jordi, Girault Jean-Antoine, Chan Susan, Kastner Philippe, Canals Josep M
Stem Cells and Regenerative Medicine Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.
Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.
Development. 2017 Apr 15;144(8):1566-1577. doi: 10.1242/dev.138248. Epub 2017 Mar 13.
Here, we unravel the mechanism of action of the Ikaros family zinc finger protein Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons, which express dopamine 2 receptor and enkephalin. To exert this effect, He is expressed in neural progenitor cells (NPCs) keeping them in the G/G phase of the cell cycle. Thus, a lack of He results in an increase of S-phase entry and S-phase length of NPCs, which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ), which end up dying at postnatal stages. Therefore, mice show a reduction in the number of dorso-medial striatal MSNs in the adult that produces deficits in motor skills acquisition. In addition, overexpression of in NPCs induces misexpression of DARPP-32 when transplanted in mouse striatum. These findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development.
在此，我们揭示了伊卡洛斯家族锌指蛋白赫利俄斯（Helios，He）在纹状体中型多棘神经元（MSNs）发育过程中的作用机制。He调节参与纹状体苍白球神经元生成的第二轮纹状体神经发生，这些神经元表达多巴胺2受体和脑啡肽。为发挥这种作用，He在神经祖细胞（NPCs）中表达，使它们处于细胞周期的G/G期。因此，He的缺失会导致NPCs进入S期的比例增加以及S期长度延长，进而损害纹状体神经发生，并在生发区（GZ）导致循环NPCs数量积累，这些NPCs最终在出生后阶段死亡。所以，成年小鼠背内侧纹状体MSNs数量减少，导致运动技能习得出现缺陷。此外，NPCs中He的过表达在移植到小鼠纹状体时会诱导DARPP - 32的错误表达。这些发现表明He参与了一部分纹状体苍白球MSNs的正常发育，并揭示了神经元发育的新细胞机制。
