Dkk2 plays an essential role in the corneal fate of the ocular surface epithelium
Tóm tắt
The Dkk family of secreted cysteine-rich proteins regulates Wnt/β-catenin signaling by interacting with the Wnt co-receptor Lrp5/6. Here, we show that Dkk2-mediated repression of the Wnt/β-catenin pathway is essential to promote differentiation of the corneal epithelial progenitor cells into a non-keratinizing stratified epithelium. Complete transformation of the corneal epithelium into a stratified epithelium that expresses epidermal-specific differentiation markers and develops appendages such as hair follicles is achieved in the absence of the Dkk2 gene function. We show that Dkk2 is a key regulator of the corneal versus epidermal fate of the ocular surface epithelium.
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Andl, T., Reddy, S. T., Gaddapara, T. and Millar, S. E.(2002). Wnt signals are required for the initiation of hair follicle development. Dev. Cell2, 643-653.
Ang, S. J., Stump, R. J. W., Lovicu, F. J. and McAvoy, J. W.(2004). Spatial and temporal expression of Wnt and Dickkopf genes during murine lens development. Gene Exp. Patterns4, 289-295.
Candi, E., Schmidt, R. and Melino, G. (2005). The cornified envelope: a model of cell death in the skin. Nat. Rev. Mol. Cell Biol. 6,328-340.
Chaloin-Dufau, C., Pavitt, I., Delorme, P. and Dhouailly, D.(1993). Identification of keratins 3 and 12 in corneal epithelium of vertebrates. Epithelial Cell Biol.2, 120-125.
Cotsarelis, G., Cheng, S. Z., Dong, G., Sun, T. T. and Lavker,R. M. (1989). Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell57,201-209.
DasGupta, R. and Fuchs, E. (1999). Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development126,4557-4568.
Davis, J., Duncan, M. K., Robison, W. G., Jr and Piatigorsky,J. (2003). Requirement for Pax6 in corneal morphogenesis: a role in adhesion. J. Cell Sci.116,2157-2167.
Ferraris, C., Chevalier, G., Favier, B., Jahoda, C. A. B. and Dhouailly, D. (2000). Adult corneal epithelium basal cells possess the capacity to activate epidermal, pilosebaceous and sweat gland genetic programs in response to embryonic dermal stimuli. Development127,5487-5495.
Glinka, A., Wu, W., Delius, H., Monaghan, A. P., Blumenstock, C. and Niehrs, C. (1998). Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature391,357-362.
Hashimoto, H., Itoh, M., Yamanaka, Y., Yamashita, S., Shimizu,T., Solnica-Krezel, L., Hibi, M. and Hirano, T. (2000). Zebrafish DKK1 functions in forebrain specification and axial mesendoderm formation. Dev. Biol.217,138-152.
He, X., Semenov, M., Tamai, K. and Zheng, X.(2004). LDL receptor-related proteins 5 and 6 in Wnt/b-catenin signaling: arrows point the way. Development131,1663-1677.
Hogan, B., Beddington, R., Costantini, F. and Lacy, E.(1994). Staining for β-galactosidase (lacZ) activity. In Manipulating the Mouse Embryo: A Laboratory Manual.2nd edn, pp. 373-375. New York: Cold Spring Harbor Laboratory Press.
Hsieh, J. C., Kodjabachian, L., Rebbert, M. L., Rattner, A.,Smallwood, P. M., Samos, C. H., Nusse, R., Dawid, I. B. and Nathans, J.(1999). A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature398,431-436.
Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G. and Birchmeier, W. (2001). β-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell105,533-545.
Jamora, C., DasGupta, R., Kocieniewski, P. and Fuchs, E.(2003). Links between signal transduction, transcription and adhesion in epithelial bud development. Nature422,317-322.
Li, X., Liu, P., Liu, W., Maye, P., Zhang, J., Zhang, Y.,Hurley, M., Guo, C., Boskey, A., Sun, L. et al. (2005). Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat. Genet.37,945-952.
Logan, C. Y. and Nusse, R. (2004). The Wnt signaling pathway in development and disease. Annu. Rev. Cell Dev. Biol.20,781-810.
Mao, B. and Niehrs, C. (2003). Kremen2 modulates Dickkopf2 activity during Wnt/LRP6 signaling. Gene302,179-183.
Megason, S. G. and McMahon, A. P. (2002). A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. Development129,2087-2098.
Monaghan, A. P., Kioschis, P., Wu, W., Zuniga, A., Bock, D.,Poustka, A., Delius, H. and Niehrs, C. (1999). Dickkopf genes are co-ordinately expressed in mesodermal lineages. Mech. Dev. 87,45-56.
Mukhopadhyay, M., Shtrom, S., Rodriguez-Esteban, C., Chen, L.,Tsukui, T., Gomer, L., Dorward, D. W., Glinka, A., Grinberg, A., Huang, S. P. et al. (2001). Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev. Cell1,423-434.
Nicolas, M., Wolfer, A., Raj, K., Kummer, J. A., Mill, P., van Noort, M., Hui, C. C., Clevers, H., Dotto, G. P. and Radtke, F.(2003). Notch1 functions as a tumor suppressor in mouse skin. Nat. Genet.33,416-421.
Pearton, D. J., Yang, Y. and Dhouailly, D.(2005). Transdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals. Proc. Natl. Acad. Sci. USA102,3714-3719.
Pellegrini, G., Golisano, O., Paterna, P., Lambiase, A., Bonini,S., Rama, P. and De Luca, M. (1999). Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface. J. Cell Biol.145,769-782.
Piccolo, S., Agius, E., Leyns, L., Bhattacharyya, S., Grunz, H.,Bouwmeester, T. and De Robertis, E. M. (1999). The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Nature397,707-710.
Puangsricharern, V. and Tseng, S. C. (1995). Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology102,1476-1485.
Ramaesh, T., Collinson, J. M., Ramaesh, K., Kaufman, M. H.,West, J. D. and Dhillon, B. (2003). Corneal abnormalities in Pax6+/– small eye mice mimic human aniridia-related keratopathy. Invest. Ophthalmol. Vis. Sci.44,1871-1878.
Rattner, A., Hsieh, J.-C., Smallwood, P. M., Gilbert, D.,Copeland, N. G., Jenkins, N. A. and Nathans, J. (1997). A family of secreted proteins contains homology to the Cysteine-rich ligand binding domain of frizzled receptors. Proc. Natl. Acad. Sci. USA94,2859-2863.
Silva-Vargas, V., Ceiso, C. L., Giangreco, A., Ofstad, T.,Prowse, D. M., Braun, K. M. and Watt, F. M. (2005).β-Catenin and Hedgehog signal strength can specify number and location of hair follicles in adult epidermis without recruitment of bulge stem cells. Dev. Cell9,121-131.
St-Jacques, B., Dassule, H. R., Karavanova, I., Botchkarev, V. A., Li, J., Danielian, P. S., McMahon. J. A., Lewis, P. M., Paus, R. and McMahon, A. P. (1998). Sonic hedgehog signaling is essential for hair development. Curr. Biol.8,1058-1068.
Watt, F. M. (2004). Unexpected Hedgehog-Wnt interactions in epithelial differentiation. Trends Mol. Med.10,577-580.
Wolosin, J. M., Budak, M. T. and Akinci, M. M. A.(2004). Ocular surface epithelial and stem cell development. Int. J. Dev. Biol.48,981-991.