{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:53:37Z","timestamp":1791287617785,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Exp Zool Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The enteric nervous system (ENS) constitutes the largest and most functionally autonomous subdivision of the peripheral nervous system in vertebrates. It orchestrates stereotyped motor programs, secretomotor reflexes, and neuroimmune responses without central input. This review synthesizes evidence from developmental biology, mucosal immunology, and comparative physiology to advance a framework of enteric allostatic plasticity: the proposition that ENS functional resilience arises not from hard\u2010wired reflex arcs but from a conserved capacity for transcriptional and morphological remodeling instructed by the local immune and microbial environment. We first examine the developmental ontogeny of enteric neurons, emphasizing vagal and sacral neural crest contributions, the GDNF\u2010RET chemotactic axis governing colonization, and the hierarchical transcriptional cascades (PHOX2B, ASCL1, HAND2) that specify cholinergic, nitrergic, and serotonergic lineages. We next dissect the molecular architecture of the mature ENS, systematizing neurochemical coding, re\u2010evaluating enteric glial heterogeneity across selected animal species, and describing structural variations in ganglionated plexuses that reflect evolutionary scaling of the gut wall. Functional circuit analysis addresses intrinsic sensory transduction via IPANs and enterochromaffin cells, the coordination of peristaltic and segmental motor patterns, and the neuroimmune circuits linking enteric neurons to muscularis macrophages and the innate lymphoid cells. Finally, we position the ENS as a central hub within bidirectional gut\u2010brain and gut\u2010immune axes, integrating microbial metabolites, stress hormones, and inflammatory signals to maintain intestinal allostasis. A comparative approach, contrasting murine, porcine, zebrafish, and human systems, is a prerequisite for distinguishing fundamental design principles from lineage\u2010specific elaborations and for translating mechanistic insights to clinical and veterinary neurogastroenterology.<\/jats:p>","DOI":"10.1002\/jez.70137","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:20:22Z","timestamp":1791285622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Enteric Nervous System: An Integrative Hub From Development to Systemic Physiology"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6985-3763","authenticated-orcid":false,"given":"Mario","family":"Cuchillo\u2010Hilario","sequence":"first","affiliation":[{"name":"Departamento de Ciencias Biol\u00f3gicas Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico Km 3.5 Carretera Teoloyucan\u2010Cuautitl\u00e1n Estado de M\u00e9xico M\u00e9xico"},{"name":"Departamento de Nutrici\u00f3n Animal Dr Fernando P\u00e9rez\u2010Gil Romo, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n (INCMNSZ) Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-6821","authenticated-orcid":false,"given":"Margarita","family":"D\u00edaz\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Nutrici\u00f3n Animal Dr Fernando P\u00e9rez\u2010Gil Romo, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n (INCMNSZ) Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0756-0404","authenticated-orcid":false,"given":"Mario Alberto","family":"Viazcan\u2010Carbajal","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biol\u00f3gicas Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico Km 3.5 Carretera Teoloyucan\u2010Cuautitl\u00e1n Estado de M\u00e9xico M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0257-0922","authenticated-orcid":false,"given":"Victor David","family":"Gonz\u00e1lez\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biol\u00f3gicas Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico Km 3.5 Carretera Teoloyucan\u2010Cuautitl\u00e1n Estado de M\u00e9xico M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20944"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200668"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43497-9"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0020-7519(01)00273-9"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adn9850"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410200406"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.775102"},{"key":"e_1_2_12_9_1","first-page":"iv12","article-title":"Development of the Enteric Nervous System. 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