title: Evidence for a role of matrix metalloproteinases and their inhibitors in primordial germ cell migration.
abstract: Understanding the mechanisms that enable migrating cells to reach their targets is of vital importance, as several pathologies, including cardiac defects and some tumours, are consequences of altered cell migration. With a view to evaluating if matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in the active migration of primordial germ cells (PGCs) from their place of origin in extra-embryonic sites towards their final destination in the developing gonads, we analysed the expression of mRNAs encoding nine MMPs and four TIMPs in migrating (E10.5) and post-migrating (E12.5) PGCs by means of quantitative polymerase chain reaction and the presence of MT1-MMP in the membrane of these cells. Our results show that PGCs express MMP-2, MMP-9, MMP-11, MT1-MMP, TIMP-1, TIMP-2 and TIMP-3 at both migrating and non-migrating stages. Comparing expression levels of MMP genes between E10.5 and E12.5 PGCs revealed higher expression in migrating PGCs of MT1- MMP (10.3-fold), MMP-2 (4.8-fold), MMP-11 (3.2-fold) and MMP-9 (2.1-fold). Similarly, the levels of TIMP gene expression were always higher in E12.5 genital ridge somatic cells: TIMP-3 (3.4-fold), TIMP-1 (2.4-fold) and TIMP-2 (1.8-fold). Moreover, the analysis at protein level showed the presence of MT1-MMP in the membrane of migrating PGCs whereas the expression of these metalloproteinase is not detected once the PGCs have reach the urogenital ridges and stop migrating. These results suggest that the change from the motile to non-motile phenotype that occurs during PGC maturation to gonocytes may be mediated in part by enhanced expression of MMPs in migrating PGCs together with higher expression of TIMPs in E12.5 genital ridges.
authors.affiliation: Laboratory of Stem Cells, Development & Cancer, Department of Cell Biology & Histology, Faculty of Medicine & Dentistry, University of the Basque Country, Leioa, Vizcaya, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Díez-Torre
authors.forename: M
authors.initials: M
authors.lastname: Díaz-Núñez
authors.forename: C
authors.initials: C
authors.lastname: Eguizábal
authors.forename: U
authors.initials: U
authors.lastname: Silván
authors.forename: J
authors.initials: J
authors.lastname: Aréchaga
mesh_terms: D000818:Animals; D002465:Cell Movement; D015870:Gene Expression; D020869:Gene Expression Profiling; D005854:Germ Cells / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice / Q000196:embryology; D012333:RNA, Messenger / Q000096:biosynthesis; D013234:Stem Cells / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases
keywords: matrix metalloproteinases; primordial germ cells; tissue inhibitors of metalloproteinases