{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:09:10Z","timestamp":1789168150730,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,9]]},"group-title":"Developmental Biology","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["R01AR080136"],"award-info":[{"award-number":["R01AR080136"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["R01AR082033E"],"award-info":[{"award-number":["R01AR082033E"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/035yf7a66","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM147406"],"award-info":[{"award-number":["R35GM147406"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Organ morphogenesis is orchestrated by precise coupling of mechanical and biochemical signals, yet how these two signals are integrated within tissue niche to regulate organ shape and size remains poorly understood. Here, using sweat gland as a tractable model of exocrine mini-organs, we demonstrate that dermal fibroblasts play a key role to translate prepatterned tissue stiffness gradients into spatial Wnt5a gradients via Piezo1-mediated mechanosensing. Following epidermal placode formation, progenitor cells collectively invaginate into the dermis, where spatiotemporally graded Wnt5a directs their sequential transition from ductal to glandular fate in softer distal dermis, specifying distinct exocrine compartments. Perturbation of dermal stiffness gradients and mechanosensing\n                  <jats:italic>in vivo<\/jats:italic>\n                  and\n                  <jats:italic>ex vivo<\/jats:italic>\n                  alters Wnt5a expression levels and gradient patterns and thereby changes the ductal length and glandular size, revealing a direct link between tissue mechanics and organ dimensions. To recapitulate this process\n                  <jats:italic>in vitro<\/jats:italic>\n                  , we engineer a microfluidic platform capable of generating robust and linear morphogen gradients in 3D, allowing duct-to-gland fate transitions to occur at a high resolution. Together, our finding identifies prepatterned stiffness gradients as a master upstream regulator of coupled mechanical-biochemical signaling, define a mechanistic framework for two-step sequential glandular morphogenesis, and offer new strategies for engineering glandular epithelia in regenerative medicine.\n                <\/jats:p>","DOI":"10.64898\/2026.09.04.748946","type":"posted-content","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:35:21Z","timestamp":1788957321000},"source":"Crossref","is-referenced-by-count":0,"title":["Prepatterned Tissue Stiffness Gradient Controls Organ shape and size"],"prefix":"10.64898","author":[{"given":"Jie","family":"Tong","sequence":"first","affiliation":[{"name":"The Hansj\u00f6rg Wyss Department of Plastic Surgery, New York University Grossman School of Medicine, New York, NY, 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Ju","family":"Lin","sequence":"additional","affiliation":[{"name":"The Hansj\u00f6rg Wyss Department of Plastic Surgery, New York University Grossman School of Medicine, New York, NY, 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanzhong","family":"Deng","sequence":"additional","affiliation":[{"name":"Tech4Health Institute, New York University Langone Health, New York, NY 10016, USA"},{"name":"Department of Biomedical Engineering, New York University, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Delliturri","sequence":"additional","affiliation":[{"name":"The Hansj\u00f6rg Wyss Department of Plastic Surgery, New York University Grossman School of Medicine, New York, NY, 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingang","family":"Xu","sequence":"additional","affiliation":[{"name":"Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA"},{"name":"Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8792-6890","authenticated-orcid":false,"given":"Sarah","family":"Millar","sequence":"additional","affiliation":[{"name":"Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA"},{"name":"Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Ito","sequence":"additional","affiliation":[{"name":"The Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, NY, 10016, USA"},{"name":"Department of Cell Biology, Regenerative Medicine Institute, New York University Grossman School of Medicine, New York, NY, 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haogang","family":"Cai","sequence":"additional","affiliation":[{"name":"Tech4Health Institute, New York University Langone Health, New York, NY 10016, USA"},{"name":"Department of Biomedical Engineering, New York University, Brooklyn, NY 11201, USA"},{"name":"Department of Radiology, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine P.","family":"Lu","sequence":"additional","affiliation":[{"name":"The Hansj\u00f6rg Wyss Department of Plastic Surgery, New York University Grossman School of Medicine, New York, NY, 10016, USA"},{"name":"Department of Cell Biology, Regenerative 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