{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:22:09Z","timestamp":1791408129048,"version":"4.3.3"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,4,20]],"date-time":"2005-04-20T00:00:00Z","timestamp":1113955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During heart organogenesis, the spatiotemporal organization of the extracellular matrix (ECM) undergoes significant remodeling. Because matrix metalloproteinases (MMPs) are known to be key regulators of cell\u2013matrix interactions, we analyzed the role(s) of MMPs, and specifically MMP\u20102, in early heart development. Both MMP\u20102 neutralizing antibody and the broad\u2010spectrum MMP inhibitor Ilomastat in a temporal manner, when applied between chick embryonic stages 5 (primitive streak stage) to stage 12 (\u223c16\u2010somites), produced severe heart tube defects. Exposure to the MMP inhibitor at stage 5 produced various degrees of cardia bifida. At the seven\u2010somite stage, MMP\u20102\/Ilomastat inhibition caused a shift in normal left\u2010right patterning of cell proliferation within the dorsal mesocardium and mesoderm of the anterior heart field that correlated with a change in looping direction. MMP inhibition at the 10\u2010 to 12\u2010somite stage resulted in an arrest of heart tube bending by inhibiting the breakdown of the dorsal mesocardial ECM. The experimental observations suggest that MMP activity regulates the coordination of early heart organogenesis by affecting ventral closure of the heart and gut tubes, asymmetric cell proliferation in the dorsal mesocardium to drive looping direction, and ECM degradation within the dorsal mesocardium allowing looping to proceed toward completion. Developmental Dynamics 233:739\u2013753, 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.20377","type":"journal-article","created":{"date-parts":[[2005,4,20]],"date-time":"2005-04-20T16:49:49Z","timestamp":1114015789000},"page":"739-753","source":"Crossref","is-referenced-by-count":79,"title":["Cardiac morphogenesis: Matrix metalloproteinase coordination of cellular mechanisms underlying heart tube formation and directionality of looping"],"prefix":"10.1002","volume":"233","author":[{"given":"Kersti K.","family":"Linask","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingda","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hong","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip 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