| First Author | Lee JH | Year | 2025 |
| Journal | Nature | Volume | 644 |
| Issue | 8075 | Pages | 164-172 |
| PubMed ID | 40437095 | Mgi Jnum | J:375496 |
| Mgi Id | MGI:8264869 | Doi | 10.1038/s41586-025-09013-y |
| Citation | Lee JH, et al. (2025) Astrocyte morphogenesis requires self-recognition. Nature 644(8075):164-172 |
| abstractText | Self-recognition is a fundamental cellular process across evolution and forms the basis of neuronal self-avoidance(1-4). 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(5-7). 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 gammaC3, a specific isoform in the Pcdhgamma family, is enriched in human and mouse astrocytes. Using genetic manipulation, we demonstrate that gammaC3 acts autonomously to regulate astrocyte morphogenesis in the mouse visual cortex. To determine whether gammaC3 proteins act by promoting recognition between processes of the same astrocyte, we generated pairs of gammaC3 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 gammaC3-null astrocyte restored normal morphology. By contrast, chimeric gammaC3 proteins individually expressed in single gammaC3-null mutant astrocytes did not. These data establish that self-recognition mediated by gammaC3 contributes to astrocyte development in the mammalian brain. |
