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Here we show that MMPs are not required for axon extension in the Drosophila embryo, but rather are specifically required for the execution of several stereotyped motor axon pathfinding decisions. The Drosophila genome contains only two MMP homologs, Mmp1 and Mmp2. We isolated Mmp1in a misexpression screen to identify molecules required for motoneuron development. Misexpression of either MMP inhibits the regulated separation\/defasciculation of motor axons at defined choice points. Conversely, motor nerves in Mmp1 and Mmp2 single mutants and Mmp1 Mmp2 double mutant embryos are loosely bundled\/fasciculated,with ectopic axonal projections. Quantification of these phenotypes reveals that the genetic requirement for Mmp1 and Mmp2 is distinct in different nerve branches, although generally Mmp2 plays the predominant role in pathfinding. Using both an endogenous MMP inhibitor and MMP dominant-negative constructs, we demonstrate that MMP catalytic activity is required for motor axon fasciculation. In support of the model that MMPs promote fasciculation, we find that the defasciculation observed when MMP activity is compromised is suppressed by otherwise elevating interaxonal adhesion - either by overexpressing Fas2 or by reducing Sema-1a dosage. These data demonstrate that MMP activity is essential for embryonic motor axon fasciculation.<\/jats:p>","DOI":"10.1242\/dev.011072","type":"journal-article","created":{"date-parts":[[2007,11,29]],"date-time":"2007-11-29T01:34:12Z","timestamp":1196300052000},"page":"95-109","source":"Crossref","is-referenced-by-count":63,"title":["Matrix metalloproteinases promote motor axon fasciculation in the<i>Drosophila<\/i>embryo"],"prefix":"10.1242","volume":"135","author":[{"given":"Crystal M.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Page-McCaw","sequence":"additional","affiliation":[{"name":"Department of Biology and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather T.","family":"Broihier","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042621112001000_REF1","doi-asserted-by":"crossref","unstructured":"Ahmed, Z., Dent, R. 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