Institut de Biologie de Développement de Marseille-Luminy, Aix-Marseille University, Marseille, France.
Nat Neurosci. 2012 Jun 24;15(8):1120-6. doi: 10.1038/nn.3142.
In the postnatal and adult mouse forebrain, a mosaic of spatially separated neural stem cells along the lateral wall of the ventricles generates defined types of olfactory bulb neurons. To understand the mechanisms underlying the regionalization of the stem cell pool, we focused on the transcription factor Pax6, a determinant of the dopaminergic phenotype in this system. We found that, although Pax6 mRNA was transcribed widely along the ventricular walls, Pax6 protein was restricted to the dorsal aspect. This dorsal restriction was a result of inhibition of protein expression by miR-7a, a microRNA (miRNA) that was expressed in a gradient opposing Pax6. In vivo inhibition of miR-7a in Pax6-negative regions of the lateral wall induced Pax6 protein expression and increased dopaminergic neurons in the olfactory bulb. These findings establish miRNA-mediated fine-tuning of protein expression as a mechanism for controlling neuronal stem cell diversity and, consequently, neuronal phenotype.
在产后和成年小鼠前脑中，沿着脑室侧壁排列的空间分离的神经干细胞嵌合体产生了特定类型的嗅球神经元。为了了解干细胞池分区化的机制，我们专注于转录因子 Pax6，这是该系统中多巴胺能表型的决定因素。我们发现，尽管 Pax6 mRNA 广泛转录于脑室壁上，但 Pax6 蛋白仅限于背侧。这种背侧限制是由 miR-7a 抑制蛋白表达的结果，miR-7a 是一种在与 Pax6 相反的梯度中表达的 microRNA (miRNA)。在侧脑室壁的 Pax6 阴性区域体内抑制 miR-7a 会诱导 Pax6 蛋白表达并增加嗅球中的多巴胺能神经元。这些发现确立了 miRNA 介导的蛋白质表达精细调控作为控制神经元干细胞多样性的机制，从而影响神经元表型。
