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While significant progress has been made, much remains unknown about the accuracy of native regenerative programs in cell replacement. Here, we capitalized on the regenerative capacity and stereotypic retinal organization of zebrafish to determine the specificity with which retinal M\u00fcller glial cells replace lost neuronal cell types. By utilizing a targeted genetic ablation technique, we restricted death to all or to distinct cone photoreceptor types (red, blue, or UV\u2010sensitive cones), enabling us to compare the composition of cones that are regenerated. We found that M\u00fcller glia produce cones of all types upon nondiscriminate ablation of these photoreceptors, or upon selective ablation of red or UV cones. Pan\u2010ablation of cones led to regeneration of the various cone types in relative abundances that resembled those of nonablated controls, that is, red\u2009&gt;\u2009green\u2009&gt;\u2009UV ~\u2009blue cones. Moreover, selective loss of red or UV cones biased production toward the cone type that was ablated. In contrast, ablation of blue cones alone largely failed to induce cone production at all, although it did induce cell division in M\u00fcller glia. The failure to produce cones upon selective elimination of blue cones may be due to their low abundance compared to other cone types. Alternatively, it may be that blue cone death alone does not trigger a change in progenitor competency to support cone genesis. Our findings add to the growing notion that cell replacement during regeneration does not perfectly mimic programs of cell generation during development.<\/jats:p>","DOI":"10.1002\/cne.24933","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T06:06:31Z","timestamp":1588053991000},"page":"2816-2830","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Conditional and biased regeneration of cone photoreceptor types in the zebrafish retina"],"prefix":"10.1002","volume":"528","author":[{"given":"Florence D.","family":"D'Orazi","sequence":"first","affiliation":[{"name":"Department Biological Structure University of Washington  Seattle Washington USA"},{"name":"Allen Institute for Brain Science  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachihiro C.","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department Biological Structure University of Washington  Seattle Washington USA"},{"name":"Technology Licensing Section Okinawa Institute of Science and Technology Graduate University  Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Darling","sequence":"additional","affiliation":[{"name":"Department Biological Structure University of Washington  Seattle Washington USA"},{"name":"Department of Biosciences Durham University  Durham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5089-6296","authenticated-orcid":false,"given":"Rachel O.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department Biological Structure University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4939-2020","authenticated-orcid":false,"given":"Takeshi","family":"Yoshimatsu","sequence":"additional","affiliation":[{"name":"Department Biological Structure University of Washington  Seattle Washington USA"},{"name":"School of Life Sciences University of Sussex  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.042308.113259"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22447"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.07.017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.05.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.061754"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1624-07.2007"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2006.04.006"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2014.02.014"},{"issue":"4","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1242\/dev.114.4.913","article-title":"Regeneration of dopaminergic neurons in goldfish retina","volume":"114","author":"Braisted J. 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