biostudies-literatureLee JHNINDS NIH HHS164-172https://www.ebi.ac.uk/biostudies/studies/S-EPMC12862983biostudies-literatureUnknown644(8075)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 γC3, a specific isoform in the Pcdhγ family, is enriched in human and mouse astrocytes. Using genetic manipulation, we demonstrateNatureAstrocyte morphogenesis requires self-recognition.PMC12862983R35 NS111583T32 NS048004Goodman KMSergeeva APMannepalli SXu RWeiner JAKhakh BSZipursky SLBahna FShapiro LAhlsen GHonig BLee JHfalseAstrocyte morphogenesis requires self-recognition.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 γC3, a specific isoform in the Pcdhγ family, is enriched in human and mouse astrocytes. Using genetic manipulation, we demonstrate2025-01-01T00:00:00Z2025 Aug2026-07-14T17:26:45.046Z2026-06-21T03:12:34.77ZS-EPMC128629834043709510.1038/s41586-025-09013-y