{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:01:33Z","timestamp":1788811293042,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["RO1 AR 047364"],"award-info":[{"award-number":["RO1 AR 047364"]}]},{"name":"National Institutes of Health (NIH)","award":["R37 AR060306"],"award-info":[{"award-number":["R37 AR060306"]}]},{"name":"National Institutes of Health (NIH)","award":["111-2917-I-006-006"],"award-info":[{"award-number":["111-2917-I-006-006"]}]},{"name":"National Institutes of Health (NIH)","award":["111-2314-B-006-52"],"award-info":[{"award-number":["111-2314-B-006-52"]}]},{"name":"Taiwan NSTC","award":["RO1 AR 047364"],"award-info":[{"award-number":["RO1 AR 047364"]}]},{"name":"Taiwan NSTC","award":["R37 AR060306"],"award-info":[{"award-number":["R37 AR060306"]}]},{"name":"Taiwan NSTC","award":["111-2917-I-006-006"],"award-info":[{"award-number":["111-2917-I-006-006"]}]},{"name":"Taiwan NSTC","award":["111-2314-B-006-52"],"award-info":[{"award-number":["111-2314-B-006-52"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JDB"],"abstract":"<jats:p>Among amniotic skin appendages, avian feathers and mammalian hairs protect their stem cells in specialized niches, located in the collar bulge and hair bulge, respectively. In chickens and alligators, label retaining cells (LRCs), which are putative stem cells, are distributed in the hinge regions of both avian scutate scales and reptilian overlapping scales. These LRCs take part in scale regeneration. However, it is unknown whether other types of scales, for example, symmetrically shaped reticulate scales, have a similar way of preserving their stem cells. In particular, the foot sole represents a special interface between animal feet and external environments, with heavy mechanical loading. This is different from scutate-scale-covered metatarsal feet that function as protection. Avian reticulate scales on foot soles display specialized characteristics in development. They do not have a placode stage and lack \u03b2-keratin expression. Here, we explore the molecular and cellular characteristics of avian reticulate scales. RNAscope analysis reveals different molecular profiles during surface and hinge determination compared with scutate scales. Furthermore, reticulate scales express Keratin 15 (K15) sporadically in both surface- and hinge-region basal layer cells, and LRCs are not localized. Upon wounding, the reticulate scale region undergoes repair but does not regenerate. Our results suggest that successful skin appendage regeneration requires localized stem cell niches to guide regeneration.<\/jats:p>","DOI":"10.3390\/jdb11030030","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T01:38:32Z","timestamp":1688434712000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular and Cellular Characterization of Avian Reticulate Scales Implies the Evo\u2013Devo Novelty of Skin Appendages in Foot Sole"],"prefix":"10.3390","volume":"11","author":[{"given":"Tzu-Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Marine Biology and Cetacean Research Center, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8899-9773","authenticated-orcid":false,"given":"Michael W.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine and Department of Life Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7523-087X","authenticated-orcid":false,"given":"Hao-Ven","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Marine Biology and Cetacean Research Center, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Cheng","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, National Taiwan University, Taipei 106216, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Ming","family":"Chuong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0035-8494","authenticated-orcid":false,"given":"Ping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1387\/ijdb.15272390","article-title":"Evo-Devo of amniote integuments and appendages","volume":"48","author":"Wu","year":"2004","journal-title":"Int. J. Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1387\/ijdb.072556cc","article-title":"Reptile scale paradigm: Evo-Devo, pattern formation and regeneration","volume":"53","author":"Chang","year":"2009","journal-title":"Int. J. Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0070-2153(05)72005-6","article-title":"Engineering stem cells into organs: Topobiological transformations demonstrated by beak, feather, and other ectodermal organ morphogenesis","volume":"72","author":"Chuong","year":"2006","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"dev.198671","DOI":"10.1242\/dev.198671","article-title":"Cyclic growth of dermal papilla and regeneration of follicular mesenchymal components during feather cycling","volume":"148","author":"Wu","year":"2021","journal-title":"Development"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cell.2004.08.012","article-title":"Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche","volume":"118","author":"Blanpain","year":"2004","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/nature04222","article-title":"Mapping stem cell activities in the feather follicle","volume":"438","author":"Yue","year":"2005","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"77S","DOI":"10.1111\/1523-1747.ep12471959","article-title":"Hair follicular stem cells: The bulge-activation hypothesis","volume":"96","author":"Sun","year":"1991","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16766-y","DOI":"10.1038\/s41598-018-35176-y","article-title":"Comprehensive molecular and cellular studies suggest avian scutate scales are secondarily derived from feathers, and more distant from reptilian scales","volume":"8","author":"Wu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_9","unstructured":"Sawyer, R.H., Knapp, L.W., and O\u2019Guin, W.M. (1986). Biology of the Integument, Springer."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13227-019-0130-9","article-title":"Conserved gene signalling and a derived patterning mechanism underlie the development of avian footpad scales","volume":"10","author":"Cooper","year":"2019","journal-title":"Evodevo"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E6770","DOI":"10.1073\/pnas.1520566112","article-title":"Topographical mapping of \u03b1- and \u03b2-keratins on developing chicken skin integuments","volume":"112","author":"Wu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","first-page":"63","article-title":"Formation of feathers on chick foot scales: A stage-dependent morphogenetic response to retinoic acid","volume":"58","author":"Dhouailly","year":"1980","journal-title":"J. Embryol. Exp. Morphol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1006\/dbio.1999.9580","article-title":"Beta-Catenin in Epithelial Morphogenesis: Conversion of Part of Avian Foot Scales into Feather Buds with a Mutated Beta-Catenin","volume":"219","author":"Widelitz","year":"2000","journal-title":"Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1006\/dbio.1997.8844","article-title":"Disruption of scale development by Delta-1 misexpression","volume":"195","author":"Crowe","year":"1998","journal-title":"Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1126\/science.272.5262.738","article-title":"Requirement for BMP signaling in interdigital apoptosis and scale formation","volume":"272","author":"Zou","year":"1996","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"eadg9619","DOI":"10.1126\/sciadv.adg9619","article-title":"Transient agonism of the sonic hedgehog pathway triggers a permanent transition of skin appendage fate in the chicken embryo","volume":"9","author":"Cooper","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/molbev\/msx295","article-title":"Multiple Regulatory Modules Are Required for Scale-to-Feather Conversion","volume":"35","author":"Wu","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1126\/science.1098109","article-title":"Molecular Shaping of the Beak","volume":"305","author":"Wu","year":"2004","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E2009","DOI":"10.1073\/pnas.1213202110","article-title":"Specialized stem cell niche enables repetitive renewal of alligator teeth","volume":"110","author":"Wu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","unstructured":"Chuong, C. (1998). Molecular Basis of Epithelial Appendage Morphogenesis, Landes Bioscience."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cub.2018.11.009","article-title":"Timed Collinear Activation of Hox Genes during Gastrulation Controls the Avian Forelimb Position","volume":"29","author":"Moreau","year":"2019","journal-title":"Curr. Biol."},{"key":"ref_22","first-page":"2850","article-title":"Data from: A transgenic quail model that enables dynamic imaging of amniote embryogenesis","volume":"142","author":"Huss","year":"2015","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1242\/dev.083113","article-title":"Lgr proteins in epithelial stem cell biology","volume":"140","author":"Barker","year":"2013","journal-title":"Development"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/nature01196","article-title":"The morphogenesis of feathers","volume":"420","author":"Yu","year":"2002","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1006\/dbio.1996.0266","article-title":"Local delivery of TGF beta2 can substitute for placode epithelium to induce mesenchymal condensation during skin appendage morphogenesis","volume":"179","author":"Chuong","year":"1996","journal-title":"Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ydbio.2012.01.026","article-title":"Sostdc1 defines the size and number of skin appendage placodes","volume":"364","author":"Tummers","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/sj.jid.5700376","article-title":"Epithelial stem cells: A folliculocentric view","volume":"126","author":"Cotsarelis","year":"2006","journal-title":"J. Investig. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1242\/jcs.111.21.3179","article-title":"The C8\/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells","volume":"111","author":"Lyle","year":"1998","journal-title":"J. Cell. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nature06457","article-title":"Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration","volume":"451","author":"Plikus","year":"2008","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/reg2.9","article-title":"Regeneration of reptilian scales after wounding: Neogenesis, regional difference, and molecular modules","volume":"1","author":"Wu","year":"2014","journal-title":"Regeneration"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.proghi.2006.01.001","article-title":"Cytochemical, biochemical and molecular aspects of the process of keratinization in the epidermis of reptilian scales","volume":"40","author":"Alibardi","year":"2006","journal-title":"Prog. Histochem. Cytochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/j.1600-0625.2007.00609.x","article-title":"Hard cornification in reptilian epidermis in comparison to cornification in mammalian epidermis","volume":"16","author":"Alibardi","year":"2007","journal-title":"Exp. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00418-018-1701-x","article-title":"Characterization of the human ridged and non-ridged skin: A comprehensive histological, histochemical and immunohistochemical analysis","volume":"151","author":"Carriel","year":"2019","journal-title":"Histochem. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"628711","DOI":"10.3389\/fnana.2021.628711","article-title":"The Anatomical Distribution of Mechanoreceptors in Mouse Hind Paw Skin and the Influence of Integrin alpha1beta1 on Meissner-Like Corpuscle Density in the Footpads","volume":"15","author":"Wai","year":"2021","journal-title":"Front. Neuroanat."}],"container-title":["Journal of Developmental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2221-3759\/11\/3\/30\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:05:11Z","timestamp":1760126711000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2221-3759\/11\/3\/30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,3]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["jdb11030030"],"URL":"https:\/\/doi.org\/10.3390\/jdb11030030","relation":{},"ISSN":["2221-3759"],"issn-type":[{"value":"2221-3759","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,3]]}}}