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Excitatory synapses are formed and matured by the cooperative actions of synaptic organizers, such as neurexins (Nrxns), neuroligins (Nlgns), LRRTMs, and Cbln1. Recent super-resolution nanoscopy developments have revealed that many synaptic organizers, as well as glutamate receptors and glutamate release machinery, exist as nanoclusters within synapses. However, it is unclear how such nanodomains interact with each other to organize excitatory synapses in vivo. By applying X10 expansion microscopy to epitope tag knockin mice, we found that Cbln1, Nlgn1, and LRRTM1, which share Nrxn as a common presynaptic receptor, form overlapping or separate nanodomains depending on Nrxn with or without a sequence encoded by splice site 4. The size and position of glutamate receptor nanodomains of GluD1, NMDA, and AMPA receptors were regulated by Cbln1, Nlgn1, and LRRTM1 nanodomains, respectively. These findings indicate that Nrxns anterogradely regulate the postsynaptic nanoscopic architecture of glutamate receptors through competition and coordination of Nrxn ligands. [Display omitted] • Expansion microscopy revealed the nanoscopic architecture of excitatory synapses • Nlgn1, LRRTM1, and Cbln1 formed nanoclusters independently of PSD-95 • The presynaptic Nrxn isoforms regulate Nlgn1, LRRTM1, and Cbln1 nanoclusters • Nlgn1, LRRTM1, and Cbln1 nanoclusters are linked to glutamate receptor subtypes Synaptic organizers, such as neuroligin1, LRRTM1, and Cbln1, commonly target neurexin. Using X10 expansion microscopy, Nozawa et al. revealed that presynaptic neurexin isoforms regulated nanoclusters of postsynaptic neurexin ligands and glutamate receptor subtypes. Their findings provide models of how neurexin ligands coordinate or compete to organize excitatory synapses in vivo. [ABSTRACT FROM AUTHOR]