{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:39:17Z","timestamp":1785436757406,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,18]]},"group-title":"Developmental Biology","reference-count":26,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01DK121706"],"award-info":[{"award-number":["R01DK121706"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Pancreatic islets regulate blood glucose homeostasis. Although islet architecture is stable under homeostatic conditions, increased metabolic demand drives compensatory islet expansion. In mice, islets are organized as a \u03b2 cell core surrounded by a mantle of \u03b1 and \u03b4 cells. The formation of islet architecture during development requires expression of Roundabout receptors 1 and 2 (Robo1\/2) in endocrine cells and of Slits 2 and 3 (Slit2\/3) from islet-extrinsic sources. Furthermore, expression of Robo2 in endocrine cells is required to maintain islet architecture in the adult mouse. However, the cellular sources of Slit2\/3 in the adult pancreas and their expression dynamics during islet expansion remain unknown. Here, we identify distinct stromal populations, including fibroblasts and pericytes, as well as neurons within intrapancreatic ganglia, as the sources of Slit2\/3. We further show that Slit3 expression is increased in Ob\/Ob mice, and that SLIT2 expression is elevated in stromal cell populations of humans with type 2 diabetes. The expression of neither Slit2 nor Slit3 was affected by deletion of Robo2 in \u03b2 cells. Together, these findings define the cellular origins of Slit2\/3 and their expression dynamics in the adult pancreas, supporting a potential role for Slit signaling in the diabetic islet microenvironment.<\/jats:p>","DOI":"10.64898\/2026.05.15.725534","type":"posted-content","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T03:55:23Z","timestamp":1779162923000},"source":"Crossref","is-referenced-by-count":0,"title":["Stromal and Neuronal Sources of Slit2\/3 Ligands in the Adult Pancreas Exhibit Distinct Expression Patterns Independent of Robo2 Receptor Expression in the Islet"],"prefix":"10.64898","author":[{"given":"Matthew R.","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Cell and Regenerative Biology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas G.","family":"Pintozzi","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn M.","family":"Schoff","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa I.","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel H.","family":"Kasper","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina G.","family":"Steele","sequence":"additional","affiliation":[{"name":"Division of gastroenterology and hepatology, Department of Internal Medicine, University of Cincinnati, College of Medicine, Cincinnati, OH, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5308-4194","authenticated-orcid":false,"given":"Barak","family":"Blum","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052104151122000_2026.05.15.725534v1.1","doi-asserted-by":"publisher","DOI":"10.4161\/isl.2.3.11815"},{"key":"2026052104151122000_2026.05.15.725534v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110384"},{"key":"2026052104151122000_2026.05.15.725534v1.3","doi-asserted-by":"crossref","unstructured":"Adams, M.T. , et al. Reduced synchroneity of intra-islet Ca(2+) oscillations in vivo in Robo-deficient beta cells. eLife 10(2021).","DOI":"10.7554\/eLife.61308"},{"key":"2026052104151122000_2026.05.15.725534v1.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152446"},{"key":"2026052104151122000_2026.05.15.725534v1.5","doi-asserted-by":"crossref","first-page":"e23106","DOI":"10.1096\/fj.202200705RR","article-title":"Disrupted glucose homeostasis and glucagon and insulin secretion defects in Robo betaKO mice","volume":"37","year":"2023","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"key":"2026052104151122000_2026.05.15.725534v1.6","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.celrep.2013.06.019","article-title":"Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation","volume":"4","year":"2013","journal-title":"Cell reports"},{"key":"2026052104151122000_2026.05.15.725534v1.7","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1369\/0022155415583535","article-title":"Alpha-, Delta- and PP-cells: Are They the Architectural Cornerstones of Islet Structure and Co-ordination?","volume":"63","year":"2015","journal-title":"The journal of histochemistry and cytochemistry: official journal of the Histochemistry Society"},{"key":"2026052104151122000_2026.05.15.725534v1.8","doi-asserted-by":"crossref","unstructured":"Adams, M.T. , Gilbert, J.M. , Hinojosa Paiz, J. , Bowman, F.M. & Blum, B . Endocrine cell type sorting and mature architecture in the islets of Langerhans require expression of Roundabout receptors in beta cells. 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