Mesman Simone, Wever Iris, Smidt Marten P
Swammerdam Institute for Life Sciences, FNWI, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
Biomedicines. 2021 Mar 20;9(3):317. doi: 10.3390/biomedicines9030317.
During development, mesodiencephalic dopaminergic (mdDA) neurons form into different molecular subsets. Knowledge of which factors contribute to the specification of these subsets is currently insufficient. In this study, we examined the role of , a member of the E-box protein family, in mdDA neuronal development and subset specification. We show that is expressed throughout development, but is no longer detected in adult midbrain. Deletion of results in an initial increase in TH-expressing neurons at E11.5, but this normalizes at later embryonic stages. However, the caudal subset marker and rostral subset marker are affected at E14.5, indicating that is involved in correct differentiation of mdDA neuronal subsets. At P0, expression of these markers partially recovers, whereas expression of transcript and TH protein appears to be affected in lateral parts of the mdDA neuronal population. The initial increase in TH-expressing cells and delay in subset specification could be due to the increase in expression of the bHLH factor , known for its role in mdDA neuronal differentiation, upon loss of . Taken together, our data identified a minor role for in mdDA neuronal development and subset specification.
在发育过程中,中脑多巴胺能(mdDA)神经元形成不同的分子亚群。目前对于哪些因素促成这些亚群的特化了解不足。在本研究中,我们研究了E-box蛋白家族成员 在mdDA神经元发育和亚群特化中的作用。我们发现 在整个发育过程中均有表达,但在成年中脑中不再检测到。缺失 在E11.5时导致表达酪氨酸羟化酶(TH)的神经元最初增加,但在胚胎后期阶段恢复正常。然而,在E14.5时,尾侧亚群标志物 和头侧亚群标志物 受到影响,表明 参与mdDA神经元亚群的正确分化。在出生后第0天(P0),这些标志物的表达部分恢复,而 在mdDA神经元群体外侧部分的转录本表达和TH蛋白表达似乎受到影响。表达TH的细胞最初增加以及亚群特化延迟可能是由于 在缺失时,已知在mdDA神经元分化中起作用的bHLH因子 的表达增加所致。综上所述,我们的数据确定了 在mdDA神经元发育和亚群特化中起次要作用。