{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:02:25Z","timestamp":1785438145184,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,29]]},"reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"award":["R01AR078050"],"award-info":[{"award-number":["R01AR078050"]}],"id":[{"id":"https:\/\/ror.org\/006zn3t30","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R37AR060306"],"award-info":[{"award-number":["R37AR060306"]}],"id":[{"id":"https:\/\/ror.org\/006zn3t30","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Tissue patterning is integral to development and regeneration, yet the factors that initiate morphogenetic patterning remain to be explored. Here, using embryonic chicken skin as a model, we show that perturbation of calcium signaling induces\n                  <jats:italic>de novo<\/jats:italic>\n                  feather bud formation in regions that normally do not form feather buds. This is achieved through coordinated changes in calcium dynamics, endogenous bioelectric currents, transcriptional regulation of calcium and potassium channel genes, and morphogen signaling. Different combinations of channel perturbations altered the number, distribution, size, and shape of induced feather buds. Live calcium imaging and extracellular electrophysiological recordings revealed homeostatic regulation, in which initially depressed calcium activity is followed by elevated calcium activity. Inward bioelectric currents emerge as\n                  <jats:italic>de novo<\/jats:italic>\n                  feather buds appear. Potassium channel blockade suppressed calcium dynamics, abolished endogenous currents, and inhibited new bud formation. Canonical feather morphogenesis pathways including Shh and \u03b2-catenin are induced in these new buds. Our findings support a model in which developmental bioelectricity contributes to regulating the threshold of feather bud formation. These results identify developmental bioelectricity as an unrecognized regulatory layer of tissue patterning that warrants further study.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Bullet points<\/jats:title>\n                  <jats:list list-type=\"simple\">\n                    <jats:list-item>\n                      <jats:p>\n                        - Calcium signaling perturbation induces\n                        <jats:italic>de novo<\/jats:italic>\n                        feather bud formation in apteric skin\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>- Ion channel perturbations regulate the formation, distribution and shape of new buds across a continuum, depending on channel type(s) and perturbation strength.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>- Elevated calcium activity and inward bioelectric currents accompany feather bud induction<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>- Developmental bioelectricity represents an unrecognized regulatory layer for morphogenesis<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.28.735123","type":"posted-content","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T21:55:12Z","timestamp":1782770112000},"source":"Crossref","is-referenced-by-count":0,"title":["Bioelectric state transitions enable\n                  <i>de novo<\/i>\n                  feather bud formation in developing skin"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8222-5614","authenticated-orcid":false,"given":"Hans I-Chen","family":"Harn","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Han","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Southern California, Los Angeles, CA, USA"},{"name":"Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, The University of Southern California, Los Angeles, CA, USA"},{"name":"Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randle B.","family":"Widelitz","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9673-3994","authenticated-orcid":false,"given":"Cheng-Ming","family":"Chuong","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Hsiu-Ping","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070202301285000_2026.06.28.735123v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-012-1329-4"},{"key":"2026070202301285000_2026.06.28.735123v1.2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02812"},{"key":"2026070202301285000_2026.06.28.735123v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2019.01.007"},{"key":"2026070202301285000_2026.06.28.735123v1.4","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/aabb18"},{"key":"2026070202301285000_2026.06.28.735123v1.5","doi-asserted-by":"publisher","DOI":"10.4161\/chan.4.6.14106"},{"key":"2026070202301285000_2026.06.28.735123v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.74"},{"key":"2026070202301285000_2026.06.28.735123v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.028"},{"key":"2026070202301285000_2026.06.28.735123v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001807"},{"key":"2026070202301285000_2026.06.28.735123v1.9","doi-asserted-by":"publisher","DOI":"10.1177\/1073858403009003011"},{"key":"2026070202301285000_2026.06.28.735123v1.10","doi-asserted-by":"crossref","unstructured":"Harn, H.I. , Davidson, J.M. , Chuong, C.M ., 2023. 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