Hattori, D. et al. Robust discrimination between self and non-self neurites requires thousands of Dscam1 isoforms. Nature 461, 644–648 (2009).
Miura, S. K., Martins, A., Zhang, K. X., Graveley, B. R. & Zipursky, S. L. Probabilistic splicing of Dscam1 establishes identity at the level of single neurons. Cell 155, 1166–1177 (2013).
Zipursky, S. L. & Grueber, W. B. The molecular basis of self-avoidance. Annu. Rev. Neurosci. 36, 547–568 (2013).
Sanes, J. R. & Zipursky, S. L. Synaptic specificity, recognition molecules, and assembly of neural circuits. Cell 181, 1434–1435 (2020).
Mountoufaris, G. et al. Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly. Science 356, 411–414 (2017).
Thu, C. A. et al. Single-cell identity generated by combinatorial homophilic interactions between α, β, and γ protocadherins. Cell 158, 1045–1059 (2014).
Lefebvre, J. L., Kostadinov, D., Chen, W. V., Maniatis, T. & Sanes, J. R. Protocadherins mediate dendritic self-avoidance in the mammalian nervous system. Nature 488, 517–521 (2012).
Chen, W. V. et al. Pcdhαc2 is required for axonal tiling and assembly of serotonergic circuitries in mice. Science 356, 406–411 (2017).
Meltzer, S. et al. γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons. Neuron 111, 1776–1794.e1710 (2023).
Garrett, A. M. et al. CRISPR/Cas9 interrogation of the mouse Pcdhg gene cluster reveals a crucial isoform-specific role for Pcdhgc4. PLoS Genet. 15, e1008554 (2019).
Mancia Leon, W. R. et al. Clustered γ-protocadherins regulate cortical interneuron programmed cell death. eLife 9, e55374 (2020).
Sanes, J. R. & Zipursky, S. L. Synaptic specificity, recognition molecules, and assembly of neural circuits. Cell 181, 536–556 (2020).
Zipursky, S. L. & Sanes, J. R. Chemoaffinity revisited: dscams, protocadherins, and neural circuit assembly. Cell 143, 343–353 (2010).
Wu, Q. & Maniatis, T. A striking organization of a large family of human neural cadherin-like cell adhesion genes. Cell 97, 779–790 (1999).
Ing-Esteves, S. & Lefebvre, J. L. γ-Protocadherins regulate dendrite self-recognition and dynamics to drive self-avoidance. Curr. Biol. 344, 4224–4239.e4 (2024).
Rubinstein, R. et al. Molecular logic of neuronal self-recognition through protocadherin domain interactions. Cell 163, 629–642 (2015).
Schreiner, D. & Weiner, J. A. Combinatorial homophilic interaction between γ-protocadherin multimers greatly expands the molecular diversity of cell adhesion. Proc. Natl Acad. Sci. USA. 107, 14893–14898 (2010).
Zhang, Y. et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34, 11929–11947 (2014).
Zhang, Y. et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 89, 37–53 (2016).
Clarke, L. E. et al. Normal aging induces A1-like astrocyte reactivity. Proc. Natl Acad. Sci. USA 115, E1896–E1905 (2018).
Esumi, S. et al. Monoallelic yet combinatorial expression of variable exons of the protocadherin-α gene cluster in single neurons. Nat. Genet. 37, 171–176 (2005).
Kaneko, R. et al. Allelic gene regulation of Pcdh-α and Pcdh-γ clusters involving both monoallelic and biallelic expression in single Purkinje cells. J. Biol. Chem. 281, 30551–30560 (2006).
Toyoda, S. et al. Developmental epigenetic modification regulates stochastic expression of clustered protocadherin genes, generating single neuron diversity. Neuron 82, 94–108 (2014).
Endo, F. et al. Molecular basis of astrocyte diversity and morphology across the CNS in health and disease. Science 378, eadc9020 (2022).
Steffen, D. M. et al. A unique role for protocadherin γC3 in promoting dendrite arborization through an Axin1-dependent mechanism. J. Neurosci. 43, 918–935 (2023).
Shigetomi, E. et al. Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses. J. Gen. Physiol. 141, 633–647 (2013).
Shigetomi, E., Kracun, S., Sofroniew, M. V. & Khakh, B. S. A genetically targeted optical sensor to monitor calcium signals in astrocyte processes. Nat. Neurosci. 13, 759–766 (2010).
Gangwani, M. R. et al. Neuronal and astrocytic contributions to Huntington’s disease dissected with zinc finger protein transcriptional repressors. Cell Rep. 42, 111953 (2023).
Zhu, X. et al. Ultrafast optical clearing method for three-dimensional imaging with cellular resolution. Proc. Natl Acad. Sci. USA 116, 11480–11489 (2019).
Clavreul, S. et al. Cortical astrocytes develop in a plastic manner at both clonal and cellular levels. Nat. Commun. 10, 4884 (2019).
Ge, W. P., Miyawaki, A., Gage, F. H., Jan, Y. N. & Jan, L. Y. Local generation of glia is a major astrocyte source in postnatal cortex. Nature 484, 376–380 (2012).
Bushong, E. A., Martone, M. E. & Ellisman, M. H. Maturation of astrocyte morphology and the establishment of astrocyte domains during postnatal hippocampal development. Int. J. Dev. Neurosci. 22, 73–86 (2004).
Molumby, M. J., Keeler, A. B. & Weiner, J. A. Homophilic protocadherin cell–cell interactions promote dendrite complexity. Cell Rep. 15, 1037–1050 (2016).
Nern, A., Pfeiffer, B. D. & Rubin, G. M. Optimized tools for multicolor stochastic labeling reveal diverse stereotyped cell arrangements in the fly visual system. Proc. Natl Acad. Sci. USA 112, E2967–E2976 (2015).
Viswanathan, S. et al. High-performance probes for light and electron microscopy. Nat. Methods 12, 568–576 (2015).
Lefebvre, J. L., Zhang, Y., Meister, M., Wang, X. & Sanes, J. R. γ-Protocadherins regulate neuronal survival but are dispensable for circuit formation in retina. Development 135, 4141–4151 (2008).
Garrett, A. M., Schreiner, D., Lobas, M. A. & Weiner, J. A. γ-Protocadherins control cortical dendrite arborization by regulating the activity of a FAK/PKC/MARCKS signaling pathway. Neuron 74, 269–276 (2012).
Garrett, A. M. & Weiner, J. A. Control of CNS synapse development by γ-protocadherin-mediated astrocyte-neuron contact. J. Neurosci. 29, 11723–11731 (2009).
Goodman, K. M. et al. Structural basis of diverse homophilic recognition by clustered α- and β-protocadherins. Neuron 90, 709–723 (2016).
Wu, W., Ahlsen, G., Baker, D., Shapiro, L. & Zipursky, S. L. Complementary chimeric isoforms reveal Dscam1 binding specificity in vivo. Neuron 74, 261–268 (2012).
Fernandez-Monreal, M. et al. γ-protocadherins are enriched and transported in specialized vesicles associated with the secretory pathway in neurons. Eur. J. Neurosci. 32, 921–931 (2010).
O’Leary, R. et al. A variable cytoplasmic domain segment is necessary for gamma-protocadherin trafficking and tubulation in the endosome/lysosome pathway. Mol. Biol. Cell 22, 4362–4372 (2011).
Goodman, K. M. et al. How clustered protocadherin binding specificity is tuned for neuronal self-/nonself-recognition. eLife 11, e72416 (2022).
Chen, Y. et al. Axin regulates dendritic spine morphogenesis through Cdc42-dependent signaling. PLoS ONE 10, e0133115 (2015).
Tadros, W. et al. Dscam proteins direct dendritic targeting through adhesion. Neuron 89, 480–493 (2016).
Millard, S. S., Flanagan, J. J., Pappu, K. S., Wu, W. & Zipursky, S. L. Dscam2 mediates axonal tiling in the Drosophila visual system. Nature 447, 720–724 (2007).
Millard, S. S., Lu, Z., Zipursky, S. L. & Meinertzhagen, I. A. Drosophila Dscam proteins regulate postsynaptic specificity at multiple-contact synapses. Neuron 67, 761–768 (2010).
Matthews, B. J. et al. Dendrite self-avoidance is controlled by Dscam. Cell 129, 593–604 (2007).
Wojtowicz, W. M., Flanagan, J. J., Millard, S. S., Zipursky, S. L. & Clemens, J. C. Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Cell 118, 619–633 (2004).
Prasad, T., Wang, X., Gray, P. A. & Weiner, J. A. A differential developmental pattern of spinal interneuron apoptosis during synaptogenesis: insights from genetic analyses of the protocadherin-γ gene cluster. Development 135, 4153–4164 (2008).
Srinivasan, R. et al. New transgenic mouse lines for selectively targeting astrocytes and studying calcium signals in astrocyte processes in situ and in vivo. Neuron 92, 1181–1195 (2016).
Platt, R. J. et al. CRISPR–Cas9 knockin mice for genome editing and cancer modeling. Cell 159, 440–455 (2014).
Yu, X. et al. Context-specific striatal astrocyte molecular responses are phenotypically exploitable. Neuron 108, 1146–1162.e1110 (2020).
Wang, Y. et al. EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization. Cell 184, 6361–6377.e6324 (2021).
Cheng, S. et al. Vision-dependent specification of cell types and function in the developing cortex. Cell 185, 311–327.e324 (2022).
Bayraktar, O. A. et al. Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nat. Neurosci. 23, 500–509 (2020).
Madeira, F. et al. Search and sequence analysis tools services from EMBL-EBI in 2022. Nucleic Acids Res. 50, W276–W279 (2022).
Robert, X. & Gouet, P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 42, W320–W324 (2014).
Schymkowitz, J. et al. The FoldX web server: an online force field. Nucleic Acids Res. 33, W382–W388 (2005).
Sergeeva, A. P. et al. DIP/Dpr interactions and the evolutionary design of specificity in protein families. Nat. Commun. 11, 2125 (2020).
