Neurexin-neuroligin cell adhesion complexes contribute to synaptotropic dendritogenesis via growth stabilization mechanisms in vivo.
Cell adhesion molecules are well characterized for mediating synapse initiation, specification, differentiation, and maturation, yet their contribution to directing dendritic arborization during early brain circuit formation remains unclear. Using two-photon time-lapse imaging of growing neurons within intact and awake embryonic Xenopus brain, we examine roles of β-neurexin (NRX) and neuroligin-1 (NLG1) in dendritic arbor development. Using methods of dynamic morphometrics for comprehensive 3D quantification of rapid dendritogenesis, we find initial trans-synaptic NRX-NLG1 adhesions confer transient morphologic stabilization independent of NMDA receptor activity, whereas persistent stabilization requires NMDA receptor-dependent synapse maturation. Disrupting NRX-NLG1 function destabilizes filopodia while reducing synaptic density and AMPA receptor mEPSC frequency. Altered dynamic growth culminates in reduced dendritic arbor complexity as neurons mature over days. These results expand the synaptotropic model of dendritogenesis to incorporate cell adhesion molecule-mediated morphological stabilization necessary for directing normal dendritic arborization, providing a potential morphological substrate for developmental cognitive impairment associated with cell adhesion molecule mutations.
Chen
Simon Xuan
SX
Department of Cellular and Physiological Sciences and the Brain Research Centre, University of British Columbia, Vancouver, BC V6T2B5, Canada.
Tari
Parisa Karimi
PK
She
Kevin
K
Haas
Kurt
K
D000818:Animals; D030801:Animals, Genetically Modified; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D021621:Imaging, Three-Dimensional / Q000379:methods; D047468:Immunoprecipitation; D007814:Larva; D008164:Luminescent Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D018613:Microscopy, Confocal / Q000379:methods; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism; D013477:Superior Colliculi / Q000254:growth & development / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D013997:Time Factors; D014981:Xenopus
D015816:Cell Adhesion Molecules, Neuronal; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D018091:Receptors, AMPA; D050825:Synaptosomal-Associated Protein 25; C093438:neuroligin 1