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Our previous studies suggest that inadequate cell migration is the primary cytological basis for the pathogenesis of microtia, however, the underlying mechanism is unclear. Here, we further demonstrate that microtia chondrocytes show a decreased directional persistence during cell migration. Directional persistence can define a leading edge associated with oriented movement, and any mistakes would affect cell function and tissue morphology. By the screening of motility\u2010related genes and subsequent confirmations, active Rac1 (Rac1\u2010GTP) is identified to be critical for the impaired directional persistence of microtia chondrocytes migration. Moreover, Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase\u2010activating proteins (GAPs) are detected, and overexpression of Tiam1 significantly upregulates the level of Rac1\u2010GTP and improves directional migration in microtia chondrocytes. Consistently, decreased expression patterns of Tiam1 and active Rac1 are found in microtia mouse models, <jats:italic>Bmp5<\/jats:italic><jats:sup><jats:italic>se<\/jats:italic><\/jats:sup><jats:italic>\/J<\/jats:italic> and <jats:italic>Prkra<\/jats:italic><jats:sup><jats:italic>lear<\/jats:italic><\/jats:sup><jats:italic>\u20103J\/GrsrJ<\/jats:italic>. Collectively, our results provide new insights into microtia development and therapeutic strategies of tissue engineering for microtia patients.<\/jats:p>","DOI":"10.1111\/jcmm.18443","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T20:52:35Z","timestamp":1717534355000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Decreased Tiam1\u2010mediated Rac1 activation is responsible for impaired directional persistence of chondrocyte migration in microtia"],"prefix":"10.1111","volume":"28","author":[{"given":"Yi","family":"Wu","sequence":"first","affiliation":[{"name":"Research Center of Plastic Surgery Hospital Chinese Academy of Medical Science &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Center of Plastic Surgery Hospital Chinese Academy 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