Kong Hee Jeong, Ryu Jae-Ho, Kim Julan, Kim Ju-Won, Seong Bomi, Whang Ilson, Park Jung Youn, Yeo Sang-Yeob
Biotechnology Research Division, National Institute of Fisheries Science, Busan, Korea.
Department of Chemical and Biological Engineering, Hanbat National University, Daejeon, Korea.
Anim Cells Syst (Seoul). 2018 Mar 7;22(2):76-81. doi: 10.1080/19768354.2018.1443494. eCollection 2018.
Mind bomb (Mib) is an E3 ubiquitin ligase that activates the Notch signaling pathway. A previous study demonstrated that the generation of late-born GABAergic neurons may be regulated by the interplay between Mib and retinoic acid (RA). However, the relationship between Mib function and the retinoid pathway during the generation of late-born motor neurons remains unclear. We investigated the differentiation of neural progenitors into motor neurons by inhibition of Notch signaling and administration of RA to embryos. The number of motor neurons in the ventral spinal cord increased or decreased depending on the temporal inhibition of Mib-mediated Notch signaling. Inhibition of the retinoid pathway by citral treatment had a synergistic effect with overexpression of Mib:EGFP on the generation of ectopic motor neurons. Additionally, the proteolytic fragment of Mib was detected in differentiated P19 cells following treatment with RA. Our observations imply that the function of Mib may be attenuated by the retinoid pathway, and that Mib-mediated Notch signaling and the retinoid pathway play critical roles in the spatiotemporal differentiation of motor neurons.
Mind bomb（Mib）是一种激活Notch信号通路的E3泛素连接酶。先前的一项研究表明，晚期生成的γ-氨基丁酸能神经元的产生可能受Mib与视黄酸（RA）之间相互作用的调节。然而，在晚期生成的运动神经元产生过程中，Mib功能与类视黄醇途径之间的关系仍不清楚。我们通过抑制Notch信号并向胚胎施用RA来研究神经祖细胞向运动神经元的分化。脊髓腹侧运动神经元的数量根据Mib介导的Notch信号的时间抑制而增加或减少。用柠檬醛处理抑制类视黄醇途径与Mib:EGFP过表达对异位运动神经元的产生具有协同作用。此外，在用RA处理后的分化P19细胞中检测到Mib的蛋白水解片段。我们的观察结果表明，类视黄醇途径可能会减弱Mib的功能，并且Mib介导的Notch信号和类视黄醇途径在运动神经元的时空分化中起关键作用。
