Sakurai Katsuyasu, Osumi Noriko
Division of Developmental Neuroscience, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
J Neurosci. 2008 Apr 30;28(18):4604-12. doi: 10.1523/JNEUROSCI.5074-07.2008.
Astrocytes serve various important functions in the CNS, but the molecular mechanisms of their generation and maturation are still enigmatic. Here, we show that Pax6, a key transcription factor that controls neurogenesis, also regulates proliferation, differentiation, and migration of astrocytes in the CNS. We first reveal that Pax6 is expressed in astrocytes during development as well as postnatally in the wild-type mouse. Astrocytes derived from Pax6 homozygous mutants (Sey/Sey) mice exhibited aberrant proliferation together with immature differentiation, both in vivo and in vitro, with higher migration potential in scratch-wound assays in vitro. Furthermore, a larger population of Sey/Sey astrocytes expresses neural stem cell markers such as nestin, Sox2, and prominin-1. These phenotypes of Pax6-deficient astrocytes putatively occur via higher Akt activity. Thus, the breakdown of Pax6 function induces the retention of neural stem-like characteristics and inhibits astrocyte maturation.
星形胶质细胞在中枢神经系统中发挥着多种重要功能，但其生成和成熟的分子机制仍然不明。在此，我们表明，Pax6作为控制神经发生的关键转录因子，也调节中枢神经系统中星形胶质细胞的增殖、分化和迁移。我们首先发现，在野生型小鼠的发育过程以及出生后，Pax6在星形胶质细胞中表达。源自Pax6纯合突变体（Sey/Sey）小鼠的星形胶质细胞在体内和体外均表现出异常增殖以及不成熟的分化，在体外划痕试验中具有更高的迁移潜力。此外，大量的Sey/Sey星形胶质细胞表达神经干细胞标志物，如巢蛋白、Sox2和prominin-1。Pax6缺陷型星形胶质细胞的这些表型可能是通过更高的Akt活性发生的。因此，Pax6功能的破坏会导致神经干细胞样特征的保留，并抑制星形胶质细胞的成熟。
