Self-recognition is a fundamental cellular process across evolution and forms the basis of neuronal self-avoidance^1,2,3,4. Clustered protocadherin (cPcdh) proteins, which comprise a large family of isoform-specific homophilic recognition molecules, have a pivotal role in the neuronal self-avoidance that is required for mammalian brain development^5,6,7. The probabilistic expression of different cPcdh isoforms confers unique identities on neurons and forms the basis for neuronal processes to discriminate between self and non-self^5,6,8. Whether this self-recognition mechanism also exists in astrocytes remains unknown. Here we report that γC3, a specific isoform in the Pcdhγ family, is enriched in human and mouse astrocytes. Using genetic manipulation, we demonstrate that γC3 acts autonomously to regulate astrocyte morphogenesis in the mouse visual cortex. To determine whether γC3 proteins act by promoting recognition between processes of the same astrocyte, we generated pairs of γC3 chimeric proteins that are capable of heterophilic binding to each other, but incapable of homophilic binding. Co-expression of complementary heterophilic binding isoform pairs in the same γC3-null astrocyte restored normal morphology. By contrast, chimeric γC3 proteins individually expressed in single γC3-null mutant astrocytes did not. These data establish that self-recognition mediated by γC3 contributes to astrocyte development in the mammalian brain.

自我识别是进化过程中的基本细胞过程，构成了神经元自我回避的基础 ^1,2,3,4。成簇的原钙粘蛋白 （cPcdh） 蛋白由一大类亚型特异性嗜性识别分子组成，在哺乳动物大脑发育所需的神经元自我回避中起着关键作用 ^5,6,7。不同 cPcdh 亚型的概率表达赋予神经元独特的身份，并构成神经元区分自我和非自我过程的基础 ^5,6,8。这种自我识别机制是否也存在于星形胶质细胞中仍然未知。在这里，我们报道了 γC3 是 Pcdhγ 家族中的一种特异性亚型，在人和小鼠星形胶质细胞中富集。利用基因作，我们证明 γC3 自主调节小鼠视觉皮层中的星形胶质细胞形态发生。为了确定 γC3 蛋白是否通过促进同一星形胶质细胞过程之间的识别而发挥作用，我们生成了一对 γC3 嵌合蛋白，它们能够彼此异亲结合，但不能进行同嗜性结合。在相同的 γC3 缺失星形胶质细胞中互补异嗜性结合亚型对的共表达 恢复了正常形态。相比之下，在单个 γC3 缺失突变星形胶质细胞中单独表达的嵌合 γC3 蛋白则没有。这些数据确定，γC3 介导的自我识别有助于哺乳动物大脑中的星形胶质细胞发育。