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Here, we analyzed cellular flows and tissue mechanics during avian skin development. We showed how novel cellular flows initiate chemo-mechanical circuits that guide epithelial protrusion, folding, invagination, and spatial cell fate specification. In the initial feather bud formation, stiff dermal condensates protrude vertically out of the locally softened epithelial sheet. As the bud elongates, it stretches the epithelial cells at the base, which mechanically activates YAP and causes the epithelial sheet to fold downward and form a stiff cylindrical wall that invaginates into the skin. This stiff epithelial tongue is essential to the compaction and formation of the tightly packed dermal papillae. These topological transformational events are mechanically interconnected, and the completion of the previous circuit initializes the next one. On the contrary, during scale development, its rigid epithelial sheet restricts dermal cell flows, preventing other further topological transformation. We generated a topological transformation model to show how the process enables the novel evolution of feather follicles.<\/jats:p>","DOI":"10.1101\/2025.10.01.679696","type":"posted-content","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T11:35:11Z","timestamp":1759318511000},"source":"Crossref","is-referenced-by-count":0,"title":["Novel Tissue Mechanics-Guided Cellular Flows Enable the Evolution of Feather Follicles"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8222-5614","authenticated-orcid":false,"given":"Hans I-Chen","family":"Harn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting-Xin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Han","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Tau","family":"Juan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsao-Chi","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Chi","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingxiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis J.","family":"Weijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin-Lin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Ming","family":"Chuong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025100320350753000_2025.10.01.679696v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1492-9"},{"key":"2025100320350753000_2025.10.01.679696v1.2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.gene.2016.06.027","article-title":"Expressed miRNAs target feather related mRNAs involved in cell signaling, cell adhesion and structure during chicken epidermal development","volume":"591","year":"2016","journal-title":"Gene"},{"key":"2025100320350753000_2025.10.01.679696v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2009.10.075"},{"key":"2025100320350753000_2025.10.01.679696v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.008"},{"key":"2025100320350753000_2025.10.01.679696v1.5","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1146\/annurev-animal-022513-114127","article-title":"Development, regeneration, and evolution of feathers","volume":"3","year":"2015","journal-title":"Annu Rev Anim Biosci"},{"key":"2025100320350753000_2025.10.01.679696v1.6","doi-asserted-by":"crossref","first-page":"4174","DOI":"10.1038\/s41467-024-48303-3","article-title":"Conserved regulatory switches for the transition from natal down to juvenile feather in birds","volume":"15","year":"2024","journal-title":"Nat Commun"},{"key":"2025100320350753000_2025.10.01.679696v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(00)00111-8"},{"key":"2025100320350753000_2025.10.01.679696v1.8","first-page":"1009","article-title":"Expression of cell-adhesion molecules in embryonic induction","volume":"101","year":"1985","journal-title":"I. 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