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. 1994 Jul 2;126(2):519–527. doi: 10.1083/jcb.126.2.519

Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps

PMCID: PMC2200019  PMID: 8034750

Abstract

Treatment of Xenopus animal pole tissue with activin results in the induction of mesodermal cell types and a dramatic elongation of the tissue. The morphogenetic movements involved in the elongation appear similar to those in normal gastrulation, which is driven by cell rearrangement and cell intercalations. We have used this system to explore the potential regulation of cell-cell adhesion and cadherin function during morphogenesis. Quantitative blastomere aggregation assays revealed that activin induction reduced the calcium-dependent adhesion between blastomeres. Activin-induced blastomeres formed smaller aggregates, and a greater proportion of the population remained as single cells compared to uninduced blastomeres. The aggregation was mediated by C-cadherin because C-cadherin was present in the blastomeres during the aggregation assay, and monoclonal antibodies against C-cadherin inhibited the calcium-dependent aggregation of blastomeres. E-cadherin was not detectable until after the completion of the assay and, therefore, does not explain the adhesive differences between induced and uninduced blastomeres. L cells stably expressing C- cadherin (LC cells) were used to demonstrate that C-cadherin activity was specifically altered after activin induction. Blastomeres induced with activin bound fewer LC cells than uninduced blastomers. L cells not expressing C-cadherin did not adhere to blastomeres. The changes in C-cadherin-mediated adhesion occurred without detectable changes in the steady-state levels of C-cadherin or the amount of C-cadherin present on the surface of the cell. Immunoprecipitation of C-cadherin and its associated catenins revealed that the ratio of C-cadherin and the catenins was not altered by activin induction. These results demonstrate that activin decreases the adhesive function of existing C- cadherin molecules on the surface of blastomeres and suggest that decreased cadherin mediated cell-cell adhesion is associated with increased morphogenetic movement.

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Selected References

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  1. Angres B., Müller A. H., Kellermann J., Hausen P. Differential expression of two cadherins in Xenopus laevis. Development. 1991 Mar;111(3):829–844. doi: 10.1242/dev.111.3.829. [DOI] [PubMed] [Google Scholar]
  2. Behrens J., Mareel M. M., Van Roy F. M., Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. doi: 10.1083/jcb.108.6.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Behrens J., Vakaet L., Friis R., Winterhager E., Van Roy F., Mareel M. M., Birchmeier W. Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J Cell Biol. 1993 Feb;120(3):757–766. doi: 10.1083/jcb.120.3.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bixby J. L., Zhang R. Purified N-cadherin is a potent substrate for the rapid induction of neurite outgrowth. J Cell Biol. 1990 Apr;110(4):1253–1260. doi: 10.1083/jcb.110.4.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Calof A. L., Lander A. D. Relationship between neuronal migration and cell-substratum adhesion: laminin and merosin promote olfactory neuronal migration but are anti-adhesive. J Cell Biol. 1991 Nov;115(3):779–794. doi: 10.1083/jcb.115.3.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen W. C., Obrink B. Cell-cell contacts mediated by E-cadherin (uvomorulin) restrict invasive behavior of L-cells. J Cell Biol. 1991 Jul;114(2):319–327. doi: 10.1083/jcb.114.2.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Choi Y. S., Gumbiner B. Expression of cell adhesion molecule E-cadherin in Xenopus embryos begins at gastrulation and predominates in the ectoderm. J Cell Biol. 1989 Jun;108(6):2449–2458. doi: 10.1083/jcb.108.6.2449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Choi Y. S., Sehgal R., McCrea P., Gumbiner B. A cadherin-like protein in eggs and cleaving embryos of Xenopus laevis is expressed in oocytes in response to progesterone. J Cell Biol. 1990 May;110(5):1575–1582. doi: 10.1083/jcb.110.5.1575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davis R. L. Mushroom bodies and Drosophila learning. Neuron. 1993 Jul;11(1):1–14. doi: 10.1016/0896-6273(93)90266-t. [DOI] [PubMed] [Google Scholar]
  10. DiMilla P. A., Stone J. A., Quinn J. A., Albelda S. M., Lauffenburger D. A. Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength. J Cell Biol. 1993 Aug;122(3):729–737. doi: 10.1083/jcb.122.3.729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fleming T. P., Johnson M. H. From egg to epithelium. Annu Rev Cell Biol. 1988;4:459–485. doi: 10.1146/annurev.cb.04.110188.002331. [DOI] [PubMed] [Google Scholar]
  12. Frixen U. H., Behrens J., Sachs M., Eberle G., Voss B., Warda A., Löchner D., Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. doi: 10.1083/jcb.113.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ginsberg D., DeSimone D., Geiger B. Expression of a novel cadherin (EP-cadherin) in unfertilized eggs and early Xenopus embryos. Development. 1991 Feb;111(2):315–325. doi: 10.1242/dev.111.2.315. [DOI] [PubMed] [Google Scholar]
  14. Ginsberg M. H., Du X., Plow E. F. Inside-out integrin signalling. Curr Opin Cell Biol. 1992 Oct;4(5):766–771. doi: 10.1016/0955-0674(92)90099-x. [DOI] [PubMed] [Google Scholar]
  15. Green J. B., New H. V., Smith J. C. Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. Cell. 1992 Nov 27;71(5):731–739. doi: 10.1016/0092-8674(92)90550-v. [DOI] [PubMed] [Google Scholar]
  16. Gumbiner B. M. Epithelial morphogenesis. Cell. 1992 May 1;69(3):385–387. doi: 10.1016/0092-8674(92)90440-n. [DOI] [PubMed] [Google Scholar]
  17. Hatta K., Takagi S., Fujisawa H., Takeichi M. Spatial and temporal expression pattern of N-cadherin cell adhesion molecules correlated with morphogenetic processes of chicken embryos. Dev Biol. 1987 Mar;120(1):215–227. doi: 10.1016/0012-1606(87)90119-9. [DOI] [PubMed] [Google Scholar]
  18. Hatta K., Takeichi M. Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature. 1986 Apr 3;320(6061):447–449. doi: 10.1038/320447a0. [DOI] [PubMed] [Google Scholar]
  19. Herzberg F., Wildermuth V., Wedlich D. Expression of XBcad, a novel cadherin, during oogenesis and early development of Xenopus. Mech Dev. 1991 Aug;35(1):33–42. doi: 10.1016/0925-4773(91)90039-9. [DOI] [PubMed] [Google Scholar]
  20. Hyafil F., Babinet C., Jacob F. Cell-cell interactions in early embryogenesis: a molecular approach to the role of calcium. Cell. 1981 Nov;26(3 Pt 1):447–454. doi: 10.1016/0092-8674(81)90214-2. [DOI] [PubMed] [Google Scholar]
  21. Jessell T. M., Melton D. A. Diffusible factors in vertebrate embryonic induction. Cell. 1992 Jan 24;68(2):257–270. doi: 10.1016/0092-8674(92)90469-s. [DOI] [PubMed] [Google Scholar]
  22. Levi G., Ginsberg D., Girault J. M., Sabanay I., Thiery J. P., Geiger B. EP-cadherin in muscles and epithelia of Xenopus laevis embryos. Development. 1991 Dec;113(4):1335–1344. doi: 10.1242/dev.113.4.1335. [DOI] [PubMed] [Google Scholar]
  23. Levi G., Gumbiner B., Thiery J. P. The distribution of E-cadherin during Xenopus laevis development. Development. 1991 Jan;111(1):159–169. doi: 10.1242/dev.111.1.159. [DOI] [PubMed] [Google Scholar]
  24. Levine E., Lee C. H., Kintner C., Gumbiner B. M. Selective disruption of E-cadherin function in early Xenopus embryos by a dominant negative mutant. Development. 1994 Apr;120(4):901–909. doi: 10.1242/dev.120.4.901. [DOI] [PubMed] [Google Scholar]
  25. Matsuyoshi N., Hamaguchi M., Taniguchi S., Nagafuchi A., Tsukita S., Takeichi M. Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. J Cell Biol. 1992 Aug;118(3):703–714. doi: 10.1083/jcb.118.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McCrea P. D., Brieher W. M., Gumbiner B. M. Induction of a secondary body axis in Xenopus by antibodies to beta-catenin. J Cell Biol. 1993 Oct;123(2):477–484. doi: 10.1083/jcb.123.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. McCrea P. D., Gumbiner B. M. Purification of a 92-kDa cytoplasmic protein tightly associated with the cell-cell adhesion molecule E-cadherin (uvomorulin). Characterization and extractability of the protein complex from the cell cytostructure. J Biol Chem. 1991 Mar 5;266(7):4514–4520. [PubMed] [Google Scholar]
  28. Nose A., Nagafuchi A., Takeichi M. Expressed recombinant cadherins mediate cell sorting in model systems. Cell. 1988 Sep 23;54(7):993–1001. doi: 10.1016/0092-8674(88)90114-6. [DOI] [PubMed] [Google Scholar]
  29. Ozawa M., Kemler R. Correct proteolytic cleavage is required for the cell adhesive function of uvomorulin. J Cell Biol. 1990 Oct;111(4):1645–1650. doi: 10.1083/jcb.111.4.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rutishauser U., Acheson A., Hall A. K., Mann D. M., Sunshine J. The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science. 1988 Apr 1;240(4848):53–57. doi: 10.1126/science.3281256. [DOI] [PubMed] [Google Scholar]
  31. Smith J. C., Symes K., Hynes R. O., DeSimone D. Mesoderm induction and the control of gastrulation in Xenopus laevis: the roles of fibronectin and integrins. Development. 1990 Feb;108(2):229–238. doi: 10.1242/dev.108.2.229. [DOI] [PubMed] [Google Scholar]
  32. Vestweber D., Gossler A., Boller K., Kemler R. Expression and distribution of cell adhesion molecule uvomorulin in mouse preimplantation embryos. Dev Biol. 1987 Dec;124(2):451–456. doi: 10.1016/0012-1606(87)90498-2. [DOI] [PubMed] [Google Scholar]
  33. Vleminckx K., Vakaet L., Jr, Mareel M., Fiers W., van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991 Jul 12;66(1):107–119. doi: 10.1016/0092-8674(91)90143-m. [DOI] [PubMed] [Google Scholar]
  34. Williams C. L., Hayes V. Y., Hummel A. M., Tarara J. E., Halsey T. J. Regulation of E-cadherin-mediated adhesion by muscarinic acetylcholine receptors in small cell lung carcinoma. J Cell Biol. 1993 May;121(3):643–654. doi: 10.1083/jcb.121.3.643. [DOI] [PMC free article] [PubMed] [Google Scholar]

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