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[P63]: Synapse formation in the enteric nervous system: Interaction between neuroligins and neurexins
Author(s) -
D'Autréaux F.,
Scheiffele P.,
Gershon T.,
Leva D.,
Chalazonitis A.,
Gershon M.D.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.126
Subject(s) - columbia university , library science , philosophy , computer science , sociology , media studies
Synaptogenesis in the developing enteric nervous system (ENS) has not previously been investigated; nevertheless, the ENS contains complex microcircuits, which enable it to control the activity of the bowel without CNS input. We tested the hypotheses that adhesive interactions between presynaptic neurexins (Nrxns) and postsynaptic neuroligins (Nlgns) function in the formation of incipient synapses within the developing mammalian ENS. Nlgn mutations have been associated with autism, which frequently affects the gut. Nrxn-Nlgn interactions play a critical role in synapse formation in the hippocampus, where their alternative splicing contributes to a trans-synaptic signaling code. We found that transcripts encoding Nlgns (1–3 in rodent; 1–4, 4Y in human) and Nrxns ( and ) are expressed in the developing and mature mouse, rat, and human gut. All of the Nlgn splice variants thus far detected in the CNS were also detected in the ENS; moreover, some splice variants were developmentally regulated. Enteric neurons in both plexuses were Nlgn-immunoreactive in the developing (rodent) and mature (rodent + human) gut as were innervated non-neuronal cells, including the interstitial cells of Cajal (ICCs) of the deep muscle plexus (the non-innervated myenteric ICCs did not express Nlgn), enteroendocrine, and goblet cells. Enteric neurons (human) were Nrxn-immunoreactive. Functional synaptogenesis was assayed by analyzing the Ca-dependent axonal uptake of FM2–10 or antibodies to the ectodomain of synaptotagmin1. Enteric neurons formed synapses with one another and with HEK cells that expressed a Nlgn1 isoform (but not with control HEK cells). Synapse formation was blocked by a soluble -Nrxn that binds to this Nlgn1 isoform, but not by a control non-binding -Nrxn. Nlgn expression, even by non-neuronal cells, therefore, is sufficient to induce enteric neurons to form synapses. It is likely that a trans-synaptic splice code contributes to enteric synaptic specificity.