Aix Marseille Univ, CNRS, IBDM, Campus de Luminy, Marseille, France.
Department of Obstetrics, Gynecology, and Reproductive Sciences and the Center for Reproductive Science and Medicine, University of California, San Diego, San Diego, United States.
Elife. 2020 Aug 7;9:e58215. doi: 10.7554/eLife.58215.
Different subtypes of interneurons, destined for the olfactory bulb, are continuously generated by neural stem cells located in the ventricular and subventricular zones along the lateral forebrain ventricles of mice. Neuronal identity in the olfactory bulb depends on the existence of defined microdomains of pre-determined neural stem cells along the ventricle walls. The molecular mechanisms underlying positional identity of these neural stem cells are poorly understood. Here, we show that the transcription factor Vax1 controls the production of two specific neuronal subtypes. First, it is directly necessary to generate Calbindin expressing interneurons from ventro-lateral progenitors. Second, it represses the generation of dopaminergic neurons by dorsolateral progenitors through inhibition of Pax6 expression. We present data indicating that this repression occurs, at least in part, via activation of microRNA miR-7.
不同亚型的中间神经元不断由位于脑室和侧脑室旁的神经干细胞产生,这些神经干细胞位于小鼠的外侧前脑脑室。嗅球中的神经元特性取决于脑室壁上预定的神经干细胞的特定微区的存在。这些神经干细胞位置特性的分子机制还了解甚少。在这里,我们表明转录因子 Vax1 控制两种特定神经元亚型的产生。首先,它直接需要从腹外侧祖细胞产生表达钙结合蛋白的中间神经元。其次,它通过抑制 Pax6 表达抑制背外侧祖细胞产生多巴胺能神经元。我们提供的数据表明,这种抑制至少部分是通过激活 microRNA miR-7 来实现的。