Development, Vol 121, Issue 2 549-560, Copyright © 1995 by Company of Biologists

JOURNAL ARTICLES

Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development

JT Yang, H Rayburn and RO Hynes
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA.

alpha 4 integrins are cell surface receptors that mediate cell-extracellular matrix (ECM) and cell-cell adhesions by interacting with fibronectin (FN) and vascular cell adhesion molecule 1 (VCAM-1), respectively. We have generated a null mutation in the gene for the alpha 4 integrin subunit. Homozygous null embryos express no alpha 4 integrins and show two unexpected defects, both of which lead to embryonic lethality. The first defect is failure of fusion of the allantois with the chorion during placentation. The second is in the development of the epicardium and coronary vessels leading to cardiac hemorrhage. Both processes clearly involve alpha 4 integrin interactions that were previously unsuspected. alpha 4 integrin and VCAM-1 are expressed at the sites of these interactions. These results raise the possibility of abortifacients targeting alpha 4 integrins, and raise serious questions about potential side effects of drugs currently being designed to block alpha 4 integrin functions in inflammation.
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				A. C. Gittenberger-de Groot, M.-P. F.M. Vrancken Peeters, M. Bergwerff, M. M.T. Mentink, and R. E. Poelmann Epicardial Outgrowth Inhibition Leads to Compensatory Mesothelial Outflow Tract Collar and Abnormal Cardiac Septation and Coronary Formation Circ. Res., November 24, 2000; 87(11): 969 - 971. [Abstract] [Full Text] [PDF]

				Y. Huo, A. Hafezi-Moghadam, and K. Ley Role of Vascular Cell Adhesion Molecule-1 and Fibronectin Connecting Segment-1 in Monocyte Rolling and Adhesion on Early Atherosclerotic Lesions Circ. Res., July 21, 2000; 87(2): 153 - 159. [Abstract] [Full Text] [PDF]

				X. Z. Huang, J. F. Wu, R. Ferrando, J. H. Lee, Y. L. Wang, R. V. Farese Jr., and D. Sheppard Fatal Bilateral Chylothorax in Mice Lacking the Integrin alpha 9beta 1 Mol. Cell. Biol., July 15, 2000; 20(14): 5208 - 5215. [Abstract] [Full Text]

				B. Nait–Oumesmar, A. B. Copperman, and R. A. Lazzarini Placental Expression and Chromosomal Localization of the Human Gcm 1 Gene J. Histochem. Cytochem., July 1, 2000; 48(7): 915 - 922. [Abstract] [Full Text]

				J. Schreiber, E. Riethmacher-Sonnenberg, D. Riethmacher, E. E. Tuerk, J. Enderich, M. R. Bösl, and M. Wegner Placental Failure in Mice Lacking the Mammalian Homolog of Glial Cells Missing, GCMa Mol. Cell. Biol., April 1, 2000; 20(7): 2466 - 2474. [Abstract] [Full Text]

				J. A. Bowen and J. S. Hunt The Role of Integrins in Reproduction Experimental Biology and Medicine, April 1, 2000; 223(4): 331 - 343. [Abstract] [Full Text] [PDF]

				M Schreiber, Z. Wang, W Jochum, I Fetka, C Elliott, and E. Wagner Placental vascularisation requires the AP-1 component fra1 Development, January 11, 2000; 127(22): 4937 - 4948. [Abstract] [PDF]

				K. Roundy, A. Kollhoff, E. J. Eichwald, J. J. Weis, and J. H. Weis Microphthalmic Mice Display a B Cell Deficiency Similar to that Seen for Mast and NK Cells J. Immunol., December 15, 1999; 163(12): 6671 - 6678. [Abstract] [Full Text] [PDF]

				P. T. Shih, M.-L. Brennan, D. K. Vora, M. C. Territo, D. Strahl, M. J. Elices, A. J. Lusis, and J. A. Berliner Blocking Very Late Antigen-4 Integrin Decreases Leukocyte Entry and Fatty Streak Formation in Mice Fed an Atherogenic Diet Circ. Res., February 19, 1999; 84(3): 345 - 351. [Abstract] [Full Text] [PDF]

				M. Ogawa, M. Kizumoto, S. Nishikawa, T. Fujimoto, H. Kodama, and S.-I. Nishikawa Expression of alpha 4-Integrin Defines the Earliest Precursor of Hematopoietic Cell Lineage Diverged From Endothelial Cells Blood, February 15, 1999; 93(4): 1168 - 1177. [Abstract] [Full Text] [PDF]

				J. A. Bowen and J. S. Hunt Expression of Cell Adhesion Molecules in Murine Placentas and a Placental Cell Line Biol Reprod, February 1, 1999; 60(2): 428 - 434. [Abstract] [Full Text] [PDF]

				M. Braun, P. Pietsch, K. Schror, G. Baumann, and S. B. Felix Cellular adhesion molecules on vascular smooth muscle cells Cardiovasc Res, February 1, 1999; 41(2): 395 - 401. [Abstract] [Full Text] [PDF]

				O. Wendling, P. Chambon, and M. Mark Retinoid X receptors are essential for early mouse development and placentogenesis PNAS, January 19, 1999; 96(2): 547 - 551. [Abstract] [Full Text] [PDF]