{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:07:26Z","timestamp":1753877246028,"version":"3.41.2"},"reference-count":97,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Amniotes show a great diversity of limb phenotypes, including limbs specialized for running, flying, swimming, and digging. Here, we have examined how this diversity is generated during limb development in 13 species using transcriptomics and in situ hybridization. The selected species show evolutionary changes in the number of phalanges and\/or loss of claws. We first looked at genes that show cyclical expression during digit development. Significantly, we find that Gdf5 cycles more rapidly in digits developing more phalanges. We identified two novel cyclically expressed genes: Ackr3 and Wnt9a. We also identified a transition point at which phalanx formation stops and claw development begins. We found that this transition point is marked by the downregulation of multiple developmental genes in the phalanx-forming region, and upregulation of claw-related genes. The timing of this transition is conserved, taking place at the same developmental stage in all digits of all species examined\u2014except in the clawless digits of the Chinese soft-shelled turtle, the crocodilians, and birds. We suggest a model based on transcriptional heterochrony, in which the frequency of phalanx formation and the timing of the phalanx\u2013claw transition are evolutionary control points open to natural selection on the phenotype. Furthermore, our model suggests that relaxation of developmental constraints on the timing of the phalanx\u2013claw transition allows the digits to develop more phalanges (hyperphalangy). This is seen in some turtles, crocodilians, and dolphins. More broadly, our findings are consistent with the hypothesis that \u201chotspots\u201d in otherwise conserved developmental pathways may be targets for evolutionary tinkering.<\/jats:p>","DOI":"10.1093\/molbev\/msaf113","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T02:14:44Z","timestamp":1749435284000},"source":"Crossref","is-referenced-by-count":0,"title":["Changes in Evolutionary Developmental Control Points in the Amniote Limb May Explain Hyperphalangy"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-7986","authenticated-orcid":false,"given":"Merijn A G","family":"de Bakker","sequence":"first","affiliation":[{"name":"Animal Science & Health, Institute of Biology Leiden (IBL), Leiden University , Leiden 2333BE ,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0625-2984","authenticated-orcid":false,"given":"Luthfi","family":"Nurhidayat","sequence":"additional","affiliation":[{"name":"Animal Science & Health, Institute of Biology Leiden (IBL), Leiden University , Leiden 2333BE ,","place":["the Netherlands"]},{"name":"Faculty of Biology, Universitas Gadjah Mada , Yogyakarta 55281 ,","place":["Indonesia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6638-5874","authenticated-orcid":false,"given":"Alisha Kiran","family":"Dijkerman","sequence":"additional","affiliation":[{"name":"Animal Science & Health, Institute of Biology Leiden (IBL), Leiden University , Leiden 2333BE ,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8070-0482","authenticated-orcid":false,"given":"Wing Yu","family":"Chung","sequence":"additional","affiliation":[{"name":"Animal Science & Health, Institute of Biology Leiden (IBL), Leiden University , Leiden 2333BE ,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7389-1118","authenticated-orcid":false,"given":"Elena C","family":"Oudesluys","sequence":"additional","affiliation":[{"name":"Animal Science & Health, Institute of Biology Leiden (IBL), Leiden University , Leiden 2333BE ,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaylah","family":"de Jager","sequence":"additional","affiliation":[{"name":"Animal Science & Health, Institute of Biology Leiden (IBL), Leiden University , Leiden 2333BE ,","place":["the 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