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The Company of Biologists
Development (237)
Abstract

During early mouse development, a single-layered epithelium is transformed into the three germ layers that are the basis of the embryonic body plan. Here we describe an ENU-induced mutation, limulus (lulu), which disrupts gastrulation and the organization of all three embryonic germ layers. Positional cloning and analysis of additional alleles show that luluis a null allele of the FERM-domain gene erythrocyte protein band 4.1-like 5(Epb4.1l5). During gastrulation, some cells in lulu mutants are trapped in the primitive streak at an intermediate stage of the epithelial-mesenchymal transition; as a result, the embryos have very little paraxial mesoderm. Epithelial layers of the later lulu embryo are also disrupted: definitive endoderm is specified but does not form a gut tube,and the neural plate is broad and forms ectopic folds rather than closing to make the neural tube. In contrast to zebrafish and Drosophila, in which orthologs of Epb4.1l5 control the apical localization and activity of Crumbs proteins, mouse Crumbs proteins are localized normally to the apical surface of the lulu mutant epiblast and neural plate. However, the defects in both the lulu primitive streak and neural plate are associated with disruption of the normal organization of the actin cytoskeleton. We propose that mouse Lulu (Epb4.1l5) helps anchor the actin-myosin contractile machinery to the membrane to allow the dynamic rearrangements of epithelia that mediate embryonic morphogenesis.

Bibliography

Lee, J. D., Silva-Gagliardi, N. F., Tepass, U., McGlade, C. J., & Anderson, K. V. (2007). The FERM protein Epb4.1l5 is required for organization of the neural plate and for the epithelial-mesenchymal transition at the primitive streak of the mouse embryo. Development, 134(11), 2007–2016.

Authors 5
  1. Jeffrey D. Lee (first)
  2. Nancy F. Silva-Gagliardi (additional)
  3. Ulrich Tepass (additional)
  4. C. Jane McGlade (additional)
  5. Kathryn V. Anderson (additional)
References 43 Referenced 71
  1. Adams, R. and Kimmel, C. (2004). Morphogenetic cellular flows during Zebrafish gastrulation. In Gastrulation: From Cells to Embryo (ed. C. D. Stern), pp.305-316. Cold Spring Harbor: Cold Spring Harbor Laboratory Press.
  2. Belo, J. A., Bouwmeester, T., Leyns, L., Kertesz, N., Gallo, M.,Follettie, M. and De Robertis, E. M. (1997). Cerberus-like is a secreted factor with neutralizing activity expressed in the anterior primitive endoderm of the mouse gastrula. Mech. Dev.68, 45-57. (10.1016/S0925-4773(97)00125-1)
  3. Berryman, M., Franck, Z. and Bretscher, A.(1993). Ezrin is concentrated in the apical microvilli of a wide variety of epithelial cells whereas moesin is found primarily in endothelial cells. J. Cell Sci.105,1025-1043. (10.1242/jcs.105.4.1025)
  4. Bretscher, A., Chambers, D., Nguyen, R. and Reczek, D.(2000). ERM-Merlin and EBP50 protein families in plasma membrane organization and function. Annu. Rev. Cell Dev. Biol.16,113-143. (10.1146/annurev.cellbio.16.1.113)
  5. Bretscher, A., Edwards, K. and Fehon, R. G.(2002). ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell Biol.3, 586-599. (10.1038/nrm882)
  6. Burdsal, C. A., Damsky, C. H. and Pedersen, R. A.(1993). The role of E-cadherin and integrins in mesoderm differentiation and migration at the mammalian primitive streak. Development118,829-844. (10.1242/dev.118.3.829)
  7. Carver, E. A., Jiang, R., Lan, Y., Oram, K. F. and Gridley,T. (2001). The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol. Cell. Biol.21,8184-8188. (10.1128/MCB.21.23.8184-8188.2001)
  8. Ciruna, B. and Rossant, J. (2001). FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. Dev. Cell1, 37-49. (10.1016/S1534-5807(01)00017-X)
  9. Damjanov, I., Damjanov, A. and Damsky, C. H.(1986). Developmentally regulated expression of the cell-cell adhesion glycoprotein cell-CAM 120/80 in peri-implantation mouse embryos and extraembryonic membranes. Dev. Biol.116,194-202. (10.1016/0012-1606(86)90056-4)
  10. García-García, M. J. and Anderson, K. V.(2003). Essential role of glycosaminoglycans in Fgf signaling during mouse gastrulation. Cell114,727-737. (10.1016/S0092-8674(03)00715-3)
  11. García-García, M. J., Eggenschwiler, J. T.,Caspary, T., Alcorn, H. L., Wyler, M. R., Huangfu, D., Rakeman, A. S., Lee, J. D., Feinberg, E. H., Timmer, J. R. et al. (2005). Analysis of mouse embryonic patterning and morphogenesis by forward genetics. Proc. Natl. Acad. Sci. USA102,5913-5919. (10.1073/pnas.0501071102)
  12. Gary, R. and Bretscher, A. (1995). Ezrin self-association involves binding of an N-terminal domain to a normally masked C-terminal domain that includes the F-actin binding site. Mol. Biol. Cell6,1061-1075. (10.1091/mbc.6.8.1061)
  13. Geldmacher-Voss, B., Reugels, A. M., Pauls, S. and Campos-Ortega, J. A. (2003). A 90-degree rotation of the mitotic spindle changes the orientation of mitoses of zebrafish neuroepithelial cells. Development130,3767-3780.
  14. Götz, M. and Huttner, W. B. (2005). The cell biology of neurogenesis. Nat. Rev. Mol. Cell Biol.6,777-788. (10.1038/nrm1739)
  15. Haigo, S. L., Hildebrand, J. D., Harland, R. M. and Wallingford,J. B. (2003). Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Curr. Biol.13,2125-2137. (10.1016/j.cub.2003.11.054)
  16. Hildebrand, J. D. (2005). Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network. J. Cell Sci.118,5191-5203. (10.1242/jcs.02626)
  17. Hogan, B. L., Blessing, M., Winnier, G. E., Suzuki, N. and Jones, C. M. (1994). Growth factors in development: the role of TGF-beta related polypeptide signalling molecules in embryogenesis. Dev. Suppl.1994,53-60. (10.1242/dev.1994.Supplement.53)
  18. Hoover, K. B. and Bryant, P. J. (2002). Drosophila Yurt is a new protein-4.1-like protein required for epithelial morphogenesis. Dev. Genes Evol.212,230-238.
  19. Hsu, Y., Willoughby, J. J., Christensen, A. K. and Jensen, A. M. (2006). Mosaic eyes is a novel component of the crumbs complex and negatively regulates photoreceptor apical size. Development133,4849-4859. (10.1242/dev.02685)
  20. Hurd, T. W., Gao, L., Roh, M. H., Macara, I. G. and Margolis,B. (2003). Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nat. Cell Biol.5,137-142. (10.1038/ncb923)
  21. Imai, F., Hirai, S., Akimoto, K., Koyama, H., Miyata, T., Ogawa,M., Noguchi, S., Sasaoka, T., Noda, T. and Ohno, S. (2006). Inactivation of aPKC{lambda} results in the loss of adherens junctions in neuroepithelial cells without affecting neurogenesis in mouse neocortex. Development133,1735-1744.
  22. Jensen, A. M. and Westerfield, M. (2004). Zebrafish mosaic eyes is a novel FERM protein required for retinal lamination and retinal pigmented epithelial tight junction formation. Curr. Biol.14,711-717. (10.1016/j.cub.2004.04.006)
  23. Jensen, A. M., Walker, C. and Westerfield, M.(2001). mosaic eyes: a zebrafish gene required in pigmented epithelium for apical localization of retinal cell division and lamination. Development128,95-105. (10.1242/dev.128.1.95)
  24. Kasarskis, A., Manova, K. and Anderson, K. V.(1998). A phenotype-based screen for embryonic lethal mutations in the mouse. Proc. Natl. Acad. Sci. USA95,7485-7490. (10.1073/pnas.95.13.7485)
  25. Koike, C., Nishida, A., Akimoto, K., Nakaya, M. A., Noda, T.,Ohno, S. and Furukawa, T. (2005). Function of atypical protein kinase C lambda in differentiating photoreceptors is required for proper lamination of mouse retina. J. Neurosci.25,10290-10298. (10.1523/JNEUROSCI.3657-05.2005)
  26. Laprise, P., Beronja, S., Silva-Gagliardi, N. F., Pellikka, M.,Jensen, A. M., McGlade, C. J. and Tepass, U. (2006). The FERM protein yurt is a negative regulatory component of the crumbs complex that controls epithelial polarity and apical membrane size. Dev. Cell11,363-374. (10.1016/j.devcel.2006.06.001)
  27. Lemmers, C., Michel, D., Lane-Guermonprez, L., Delgrossi, M. H.,Medina, E., Arsanto, J. P. and Le Bivic, A. (2004). CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells. Mol. Biol. Cell15,1324-1333. (10.1091/mbc.e03-04-0235)
  28. Liu, S. C., Derick, L. H. and Palek, J. (1987). Visualization of the hexagonal lattice in the erythrocyte membrane skeleton. J. Cell Biol.104,527-536. (10.1083/jcb.104.3.527)
  29. Makarova, O., Roh, M. H., Liu, C. J., Laurinec, S. and Margolis,B. (2003). Mammalian Crumbs3 is a small transmembrane protein linked to protein associated with Lin-7 (Pals1). Gene302, 21-29. (10.1016/S0378111902010843)
  30. Mangeat, P., Roy, C. and Martin, M. (1999). ERM proteins in cell adhesion and membrane dynamics. Trends Cell Biol.9,187-192. (10.1016/S0962-8924(99)01544-5)
  31. Matsui, T., Maeda, M., Doi, Y., Yonemura, S., Amano, M.,Kaibuchi, K., Tsukita, S. and Tsukita, S. (1998). Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association. J. Cell Biol.140,647-657. (10.1083/jcb.140.3.647)
  32. McClatchey, A. I., Saotome, I., Ramesh, V., Gusella, J. F. and Jacks, T. (1997). The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. Genes Dev.11,1253-1265. (10.1101/gad.11.10.1253)
  33. Morales, F. C., Takahashi, Y., Kreimann, E. L. and Georgescu, M. M. (2004). Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 organizes ERM proteins at the apical membrane of polarized epithelia. Proc. Natl. Acad. Sci. USA101,17705-17710. (10.1073/pnas.0407974101)
  34. Omori, Y. and Malicki, J. (2006). oko meduzy and related crumbs genes are determinants of apical cell features in the vertebrate embryo. Curr. Biol.16,945-957. (10.1016/j.cub.2006.03.058)
  35. Radice, G. L., Rayburn, H., Matsunami, H., Knudsen, K. A.,Takeichi, M. and Hynes, R. O. (1997). Developmental defects in mouse embryos lacking N-cadherin. Dev. Biol.181, 64-78. (10.1006/dbio.1996.8443)
  36. Shook, D. and Keller, R. (2003). Mechanisms,mechanics and function of epithelial-mesenchymal transitions in early development. Mech. Dev.120,1351-1383. (10.1016/j.mod.2003.06.005)
  37. Tam, P. P. and Gad, J. M. (2004). Gastrulation in the mouse embryo. In Gastrulation: From Cells to Embryo (ed. C. D. Stern), pp. 233-262. Cold Spring Harbor: Cold Spring Harbor Laboratory Press.
  38. Tepass, U., Theres, C. and Knust, E. (1990). crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell61,787-799. (10.1016/0092-8674(90)90189-L)
  39. Tsukita, S. and Yonemura, S. (1999). Cortical actin organization: lessons from ERM (ezrin/radixin/moesin) proteins. J. Biol. Chem.274,34507-34510. (10.1074/jbc.274.49.34507)
  40. Wei, X. and Malicki, J. (2002). nagie oko,encoding a MAGUK-family protein, is essential for cellular patterning of the retina. Nat. Genet.31,150-157. (10.1038/ng883)
  41. Wodarz, A., Hinz, U., Engelbert, M. and Knust, E.(1995). Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell82,67-76. (10.1016/0092-8674(95)90053-5)
  42. Yamada, T., Pfaff, S. L., Edlund, T. and Jessell, T. M.(1993). Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate. Cell73,673-686. (10.1016/0092-8674(93)90248-O)
  43. Zohn, I. E., Li, Y., Skolnik, E. Y., Anderson, K. V., Han, J. and Niswander, L. (2006). p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation. Cell125,957-969. (10.1016/j.cell.2006.03.048)
Dates
Type When
Created 18 years, 3 months ago (May 16, 2007, 1:29 p.m.)
Deposited 2 years, 3 months ago (May 11, 2023, 6 p.m.)
Indexed 3 months ago (May 26, 2025, 1:05 p.m.)
Issued 18 years, 2 months ago (June 1, 2007)
Published 18 years, 2 months ago (June 1, 2007)
Published Print 18 years, 2 months ago (June 1, 2007)
Funders 0

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@article{Lee_2007, title={The FERM protein Epb4.1l5 is required for organization of the neural plate and for the epithelial-mesenchymal transition at the primitive streak of the mouse embryo}, volume={134}, ISSN={0950-1991}, url={http://dx.doi.org/10.1242/dev.000885}, DOI={10.1242/dev.000885}, number={11}, journal={Development}, publisher={The Company of Biologists}, author={Lee, Jeffrey D. and Silva-Gagliardi, Nancy F. and Tepass, Ulrich and McGlade, C. Jane and Anderson, Kathryn V.}, year={2007}, month=jun, pages={2007–2016} }