Development, Vol 128, Issue 4 459-469, Copyright © 2001 by Company of Biologists

JOURNAL ARTICLES

Rescuing the N-cadherin knockout by cardiac-specific expression of N- or E-cadherin

Y Luo, M Ferreira-Cornwell, H Baldwin, I Kostetskii, J Lenox, M Lieberman and G Radice
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Cell-cell adhesion mediated by some members of the cadherin family is essential for embryonic survival. The N-cadherin-null embryo dies during mid-gestation, with multiple developmental defects. We show that N-cadherin-null embryos expressing cadherins using muscle-specific promoters, alpha- or beta-myosin heavy chain, are partially rescued. Somewhat surprisingly, either N-cadherin or E-cadherin was effective in rescuing the embryos. The rescued embryos exhibited an increased number of somites, branchial arches and the presence of forelimb buds; however, in contrast, brain development was severely impaired. In rescued animals, the aberrant yolk sac morphology seen in N-cadherin-null embryos was corrected, demonstrating that this phenotype was secondary to the cardiac defect. Dye injection studies and analysis of chimeric animals that have both wild-type and N-cadherin-null cells support the conclusion that obstruction of the cardiac outflow tract represents a major defect that is likely to be the primary cause of pericardial swelling seen in null embryos. Although rescued embryos were more developed than null embryos, they were smaller than wild-type embryos, even though the integrity of the cardiovascular system appeared normal. The smaller size of rescued embryos may be due, at least in part, to increased apoptosis observed in tissues not rescued by transgene expression, indicating that N-cadherin-mediated cell adhesion provides an essential survival signal for embryonic cells. Our data provide in vivo evidence that cadherin adhesion is essential for cell survival and for normal heart development. Our data also show that E-cadherin can functionally substitute for N-cadherin during cardiogenesis, suggesting a critical role for cadherin-mediated cell-cell adhesion, but not cadherin family member-specific signaling, at the looping stage of heart development.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. Stepniak, G. L. Radice, and V. Vasioukhin Adhesive and Signaling Functions of Cadherins and Catenins in Vertebrate Development Cold Spring Harb Perspect Biol, November 1, 2009; 1(5): a002949 - a002949. [Abstract] [Full Text] [PDF]

				A. N. Smith, L.-A. Miller, G. Radice, R. Ashery-Padan, and R. A. Lang Stage-dependent modes of Pax6-Sox2 epistasis regulate lens development and eye morphogenesis Development, September 1, 2009; 136(17): 2977 - 2985. [Abstract] [Full Text] [PDF]

				P. Sasse, D. Malan, M. Fleischmann, W. Roell, E. Gustafsson, T. Bostani, Y. Fan, T. Kolbe, M. Breitbach, K. Addicks, et al. Perlecan is critical for heart stability Cardiovasc Res, December 1, 2008; 80(3): 435 - 444. [Abstract] [Full Text] [PDF]

				E. A. V. Jones, L. Yuan, C. Breant, R. J. Watts, and A. Eichmann Separating genetic and hemodynamic defects in neuropilin 1 knockout embryos Development, July 15, 2008; 135(14): 2479 - 2488. [Abstract] [Full Text] [PDF]

				E. A. Gustafson-Wagner, H. W. Sinn, Y.-L. Chen, D.-Z. Wang, R. S. Reiter, J. L.-C. Lin, B. Yang, R. A. Williamson, J. Chen, C.-I. Lin, et al. Loss of mXin{alpha}, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2680 - H2692. [Abstract] [Full Text] [PDF]

				J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson Vascular remodeling of the mouse yolk sac requires hemodynamic force Development, September 15, 2007; 134(18): 3317 - 3326. [Abstract] [Full Text] [PDF]

				N. G. Kan, M. P. Stemmler, D. Junghans, B. Kanzler, W. N. de Vries, M. Dominis, and R. Kemler Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm Development, January 1, 2007; 134(1): 31 - 41. [Abstract] [Full Text] [PDF]

				S. Babb-Clendenon, Y.-c. Shen, Q. Liu, K. E. Turner, M. S. Mills, G. W. Cook, C. A. Miller, V. H. Gattone II, K. F. Barald, and J. A. Marrs Cadherin-2 participates in the morphogenesis of the zebrafish inner ear J. Cell Sci., December 15, 2006; 119(24): 5169 - 5177. [Abstract] [Full Text] [PDF]

				A. K. Prakasam, V. Maruthamuthu, and D. E. Leckband Similarities between heterophilic and homophilic cadherin adhesion PNAS, October 17, 2006; 103(42): 15434 - 15439. [Abstract] [Full Text] [PDF]

				Y. Luo and G. L. Radice N-cadherin acts upstream of VE-cadherin in controlling vascular morphogenesis J. Cell Biol., April 11, 2005; 169(1): 29 - 34. [Abstract] [Full Text] [PDF]

				J. Edsbagge, J. K. Johansson, F. Esni, Y. Luo, G. L. Radice, and H. Semb Vascular function and sphingosine-1-phosphate regulate development of the dorsal pancreatic mesenchyme Development, March 1, 2005; 132(5): 1085 - 1092. [Abstract] [Full Text] [PDF]

				I. Kostetskii, J. Li, Y. Xiong, R. Zhou, V. A. Ferrari, V. V. Patel, J. D. Molkentin, and G. L. Radice Induced Deletion of the N-Cadherin Gene in the Heart Leads to Dissolution of the Intercalated Disc Structure Circ. Res., February 18, 2005; 96(3): 346 - 354. [Abstract] [Full Text] [PDF]

				J. Hatakeyama, Y. Bessho, K. Katoh, S. Ookawara, M. Fujioka, F. Guillemot, and R. Kageyama Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation Development, November 15, 2004; 131(22): 5539 - 5550. [Abstract] [Full Text] [PDF]

				C. Huang, F. Sheikh, M. Hollander, C. Cai, D. Becker, P.-H. Chu, S. Evans, and J. Chen Embryonic atrial function is essential for mouse embryogenesis, cardiac morphogenesis and angiogenesis Development, December 15, 2003; 130(24): 6111 - 6119. [Abstract] [Full Text] [PDF]

				K. L. Fritz-Six, P. R. Cox, R. S. Fischer, B. Xu, C. C. Gregorio, H. Y. Zoghbi, and V. M. Fowler Aberrant myofibril assembly in tropomodulin1 null mice leads to aborted heart development and embryonic lethality J. Cell Biol., December 8, 2003; 163(5): 1033 - 1044. [Abstract] [Full Text] [PDF]

				P. B. Bushdid, H. Osinska, R. R. Waclaw, J. D. Molkentin, and K. E. Yutzey NFATc3 and NFATc4 Are Required for Cardiac Development and Mitochondrial Function Circ. Res., June 27, 2003; 92(12): 1305 - 1313. [Abstract] [Full Text] [PDF]

				I. Masai, Z. Lele, M. Yamaguchi, A. Komori, A. Nakata, Y. Nishiwaki, H. Wada, H. Tanaka, Y. Nojima, M. Hammerschmidt, et al. N-cadherin mediates retinal lamination, maintenance of forebrain compartments and patterning of retinal neurites Development, June 1, 2003; 130(11): 2479 - 2494. [Abstract] [Full Text] [PDF]

				Y. Luo and G. L. Radice Cadherin-mediated adhesion is essential for myofibril continuity across the plasma membrane but not for assembly of the contractile apparatus J. Cell Sci., April 15, 2003; 116(8): 1471 - 1479. [Abstract] [Full Text] [PDF]

				Z. Lele, A. Folchert, M. Concha, G.-J. Rauch, R. Geisler, F. Rosa, S. W. Wilson, M. Hammerschmidt, and L. Bally-Cuif parachute/n-cadherin is required for morphogenesis and maintained integrity of the zebrafish neural tube Development, March 9, 2003; 129(14): 3281 - 3294. [Abstract] [Full Text] [PDF]

				N. P.Y. Lee, D. Mruk, W. M. Lee, and C. Y. Cheng Is the Cadherin/Catenin Complex a Functional Unit of Cell-Cell Actin-Based Adherens Junctions in the Rat Testis? Biol Reprod, February 1, 2003; 68(2): 489 - 508. [Abstract] [Full Text] [PDF]

				C. Y. Cheng and D. D. Mruk Cell Junction Dynamics in the Testis: Sertoli-Germ Cell Interactions and Male Contraceptive Development Physiol Rev, October 1, 2002; 82(4): 825 - 874. [Abstract] [Full Text] [PDF]

				M. C. Ferreira-Cornwell, Y. Luo, N. Narula, J. M. Lenox, M. Lieberman, and G. L. Radice Remodeling the intercalated disc leads to cardiomyopathy in mice misexpressing cadherins in the heart J. Cell Sci., April 15, 2002; 115(8): 1623 - 1634. [Abstract] [Full Text] [PDF]

				C. M. Niessen and B. M. Gumbiner Cadherin-mediated cell sorting not determined by binding or adhesion specificity J. Cell Biol., January 21, 2002; 156(2): 389 - 400. [Abstract] [Full Text] [PDF]

				D. S. Sohal, M. Nghiem, M. A. Crackower, S. A. Witt, T. R. Kimball, K. M. Tymitz, J. M. Penninger, and J. D. Molkentin Temporally Regulated and Tissue-Specific Gene Manipulations in the Adult and Embryonic Heart Using a Tamoxifen-Inducible Cre Protein Circ. Res., July 6, 2001; 89(1): 20 - 25. [Abstract] [Full Text] [PDF]