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The molecular mechanisms driving this shift remain largely unexplored. Here, we perform single-cell RNA sequencing (scRNA-Seq) and chromatin accessibility profiling (scATAC-Seq) across developmental retinal neurogenesis in the 13-lined ground squirrel (13LGS) to uncover the regulatory basis of this adaptation. We find that 13LGS cone photoreceptors arise not only from early-stage neurogenic progenitors, as seen in rod-dominant species like mice, but also from late-stage neurogenic progenitors. This extended period of cone generation is driven by a heterochronic shift in transcription factor expression, with cone-promoting factors such as\n                  <jats:italic>Onecut2<\/jats:italic>\n                  ,\n                  <jats:italic>Pou2f1<\/jats:italic>\n                  , and\n                  <jats:italic>Zic3<\/jats:italic>\n                  remaining active in late-stage progenitors, and factors that promote cone differentiation such as\n                  <jats:italic>Thrb<\/jats:italic>\n                  ,\n                  <jats:italic>Rxrg<\/jats:italic>\n                  , and\n                  <jats:italic>Mef2c<\/jats:italic>\n                  expressed precociously in late-stage neurogenic progenitors. Functional analyses reveal that\n                  <jats:italic>Zic3<\/jats:italic>\n                  and\n                  <jats:italic>Mef2c<\/jats:italic>\n                  are sufficient to promote cone and repress rod photoreceptor-specific gene expression, and act through species-specific regulatory elements that drive their expression in late-stage progenitors. These results demonstrate that modifications to gene regulatory networks underlie the development of cone-dominant retinas, and provide insight into mechanisms of sensory adaptation and potential strategies for cone photoreceptor regeneration in vision disorders.\n                <\/jats:p>","DOI":"10.1101\/2025.04.25.650540","type":"posted-content","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T23:23:03Z","timestamp":1746055383000},"source":"Crossref","is-referenced-by-count":0,"title":["Heterochronic transcription factor expression drives cone-dominant retina development in 13-lined ground squirrels"],"prefix":"10.64898","author":[{"given":"Kurt","family":"Weir","sequence":"first","affiliation":[{"name":"Solomon H. 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