![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 12, Issue 5, 1457-1466, May 2001
3-induced Palatogenesis Requires Matrix Metalloproteinases
§ and
*Division of Hematology-Oncology, Department of Pediatrics;
Cleft lip and palate syndromes are among the most common congenital
malformations in humans. Mammalian palatogenesis is a complex process
involving highly regulated interactions between epithelial and
mesenchymal cells of the palate to permit correct positioning of the
palatal shelves, the remodeling of the extracellular matrix (ECM), and
subsequent fusion of the palatal shelves. Here we show that several
matrix metalloproteinases (MMPs), including a cell membrane-associated
MMP (MT1-MMP) and tissue inhibitor of metalloproteinase-2 (TIMP-2) were
highly expressed by the medial edge epithelium (MEE). MMP-13 was
expressed both in MEE and in adjacent mesenchyme, whereas gelatinase A
(MMP-2) was expressed by mesenchymal cells neighboring the MEE.
Transforming growth factor (TGF)-Department of Biochemistry and Molecular Biology; and
Developmental Biology Program, Department of Pathology,
Childrens Hospital Los Angeles and the Keck School of Medicine of the
University of Southern California, Los Angeles, California 90027
3-deficient mice, which suffer from
clefting of the secondary palate, showed complete absence of TIMP-2 in
the midline and expressed significantly lower levels of MMP-13 and slightly reduced levels of MMP-2. In concordance with these findings, MMP-13 expression was strongly induced by TGF-3 in palatal
fibroblasts. Finally, palatal shelves from prefusion wild-type mouse
embryos cultured in the presence of a synthetic inhibitor of MMPs or
excess of TIMP-2 failed to fuse and MEE cells did not
transdifferentiate, phenocopying the defect of the TGF-3-deficient
mice. Our observations indicate for the first time that the proteolytic
degradation of the ECM by MMPs is a necessary step for palatal fusion.
Current address: MMP Unit, National Institute of
Dental and Craniofacial Research, Bethesda, MD 20892.
This article has been cited by other articles:
|
|
 |
|
  R. J. Richardson, J. Dixon, R. Jiang, and M. J. Dixon Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence Hum. Mol. Genet., July 15, 2009; 18(14): 2632 - 2642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Yu, L.-B. Ruest, and K. K. H. Svoboda Regulation of Epithelial-Mesenchymal Transition in Palatal Fusion Experimental Biology and Medicine, May 1, 2009; 234(5): 483 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Meng, Z. Bian, R. Torensma, and J.W. Von den Hoff Biological Mechanisms in Palatogenesis and Cleft Palate Journal of Dental Research, January 1, 2009; 88(1): 22 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, E.N. Lamme, R.P.M. Steegers-Theunissen, I.P.C. Krapels, Z. Bian, H. Marres, P.H.M. Spauwen, A.M. Kuijpers-Jagtman, and J.W. Von den Hoff Cleft Palate Cells Can Regenerate a Palatal Mucosa in vitro Journal of Dental Research, August 1, 2008; 87(8): 788 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Laffin, E. Wellberg, H.-I. Kwak, R. C. Burghardt, R. P. Metz, T. Gustafson, P. Schedin, and W. W. Porter Loss of Singleminded-2s in the Mouse Mammary Gland Induces an Epithelial-Mesenchymal Transition Associated with Up-Regulation of Slug and Matrix Metalloprotease 2 Mol. Cell. Biol., March 15, 2008; 28(6): 1936 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Verstappen and J.W. Von den Hoff Tissue Inhibitors of Metalloproteinases (TIMPs): Their Biological Functions and Involvement in Oral Disease Journal of Dental Research, December 1, 2006; 85(12): 1074 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Z. Jin and J. Ding Analysis of cell migration, transdifferentiation and apoptosis during mouse secondary palate fusion Development, September 1, 2006; 133(17): 3341 - 3347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kang and K.K.H. Svoboda Epithelial-Mesenchymal Transformation during Craniofacial Development Journal of Dental Research, August 1, 2005; 84(8): 678 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Curino, L. H. Engelholm, S. S. Yamada, K. Holmbeck, L. R. Lund, A. A. Molinolo, N. Behrendt, B. S. Nielsen, and T. H. Bugge Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy J. Cell Biol., June 20, 2005; 169(6): 977 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Perez, D. A. Cano, T. Dao-Pick, J.-P. Rougier, Z. Werb, and M. Hebrok Matrix Metalloproteinases 2 and 9 Are Dispensable for Pancreatic Islet Formation and Function In Vivo Diabetes, March 1, 2005; 54(3): 694 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Holmbeck, P. Bianco, I. Pidoux, S. Inoue, R. C. Billinghurst, W. Wu, K. Chrysovergis, S. Yamada, H. Birkedal-Hansen, and A. R. Poole The metalloproteinase MT1-MMP is required for normal development and maintenance of osteocyte processes in bone J. Cell Sci., January 1, 2005; 118(1): 147 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Kaartinen, M. Dudas, A. Nagy, S. Sridurongrit, M. M. Lu, and J. A. Epstein Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells Development, July 15, 2004; 131(14): 3481 - 3490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Stanier and G. E. Moore Genetics of cleft lip and palate: syndromic genes contribute to the incidence of non-syndromic clefts Hum. Mol. Genet., April 1, 2004; 13(suppl_1): R73 - R81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Cuervo and L. Covarrubias Death is the major fate of medial edge epithelial cells and the cause of basal lamina degradation during palatogenesis Development, January 1, 2004; 131(1): 15 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Holmbeck, P. Bianco, K. Chrysovergis, S. Yamada, and H. Birkedal-Hansen MT1-MMP-dependent, apoptotic remodeling of unmineralized cartilage: a critical process in skeletal growth J. Cell Biol., November 10, 2003; 163(3): 661 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.L. Brown, S.J. Yarram, J.P. Mansell, and J.R. Sandy Matrix Metalloproteinases have a Role in Palatogenesis Journal of Dental Research, December 1, 2002; 81(12): 826 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Netzel-Arnett, D. J. Mitola, S. S. Yamada, K. Chrysovergis, K. Holmbeck, H. Birkedal-Hansen, and T. H. Bugge Collagen Dissolution by Keratinocytes Requires Cell Surface Plasminogen Activation and Matrix Metalloproteinase Activity J. Biol. Chem., November 15, 2002; 277(47): 45154 - 45161. [Abstract] [Full Text] [PDF]
|
|
