{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T03:57:04Z","timestamp":1776743824360,"version":"3.51.2"},"reference-count":64,"publisher":"The Royal Society","issue":"95","license":[{"start":{"date-parts":[[2014,6,6]],"date-time":"2014-06-06T00:00:00Z","timestamp":1402012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["J. R. Soc. Interface."],"published-print":{"date-parts":[[2014,6,6]]},"abstract":"<jats:p>The development of the vertebral column starts with the formation of a linear array of mesenchymal condensations, forming the blueprint for the eventual alternating pattern of bone and cartilage. Despite growing insight into the molecular mechanisms of morphogenesis, the impact of the physical aspects of the environment is not well understood. We hypothesized that geometric boundary conditions may play a pivotal role in the linear patterning of condensations, as neighbouring tissues provide physical constraints to the cell population. To study the process of condensation and the patterning thereof under tightly controlled geometric constraints, we developed a novel<jats:italic>in vitro<\/jats:italic>model that combines micropatterning with the established micromass assay. The spacing and alignment of condensations changed with the width of the cell adhesive patterns, a phenomenon that could not be explained by cell availability alone. Moreover, the extent of chondrogenic commitment was increased on substrates with tighter geometric constraints. When the<jats:italic>in vivo<\/jats:italic>pattern of condensations was investigated in the developing vertebral column of chicken embryos, the measurements closely fit into the quantitative relation between geometric constraints and inter-condensation distance found<jats:italic>in vitro<\/jats:italic>. Together, these findings suggest a potential role of geometric constraints in skeletal patterning in a cellular process of self-organization.<\/jats:p>","DOI":"10.1098\/rsif.2014.0215","type":"journal-article","created":{"date-parts":[[2014,4,9]],"date-time":"2014-04-09T09:21:55Z","timestamp":1397035315000},"page":"20140215","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Linear patterning of mesenchymal condensations is modulated by geometric constraints"],"prefix":"10.1098","volume":"11","author":[{"given":"Darinka D.","family":"Klumpers","sequence":"first","affiliation":[{"name":"School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA"},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA"},{"name":"Department of Orthopedic Surgery, Research Institute MOVE, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo S.","family":"Mao","sequence":"additional","affiliation":[{"name":"School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA"},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theo H.","family":"Smit","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Research Institute MOVE, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Mooney","sequence":"additional","affiliation":[{"name":"School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA"},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2014,6,6]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.20185"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.052044di"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.024166"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1389.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2592"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10277"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1238842"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.052056lb"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006591107"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0ib00040j"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004290000114"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.006403"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.1999.0306"},{"key":"e_1_3_3_15_2","first-page":"255","article-title":"Earliest evidence of cartilage and bone development in embryonic life","volume":"255","author":"Hall BK","year":"1987","journal-title":"Clin. 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