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We found that S1P-related genes are highly expressed by retinal neurons and glia, and levels of expression were dynamically regulated following retinal damage. Drug treatments that activate S1P receptor 1 (S1PR1) or increase levels of S1P suppressed the formation of MGPCs. Conversely, treatments that inhibit S1PR1 or decrease levels of S1P stimulated the formation of MGPCs. Inhibition of S1P receptors or S1P synthesis significantly enhanced the neuronal differentiation of the progeny of MGPCs. We report that S1P-related gene expression in MG is modulated by microglia and inhibition of S1P receptors or S1P synthesis partially rescues the loss of MGPC formation in damaged retinas missing microglia. Finally, we show that TGF\u03b2\/Smad3 signaling in the resting retina maintains S1PR1 expression in MG. We conclude that the S1P signaling is dynamically regulated in MG and MGPCs in the chick retina, and activation of S1P signaling depends, in part, on signals produced by reactive microglia.<\/jats:p>","DOI":"10.7554\/elife.102151","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T11:25:42Z","timestamp":1732706742000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.102151","source":"Crossref","is-referenced-by-count":4,"title":["Sphingosine-1-phosphate signaling regulates the ability of M\u00fcller glia to become neurogenic, proliferating progenitor-like cells"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6827-0552","authenticated-orcid":true,"given":"Olivia B","family":"Taylor","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rs6vg23","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, College of Medicine, The Ohio State University","place":["Columbus, United 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