SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes

Journal of Cell Biology

Volumn 166, Issue 1, 2004, Pages 37-47

  Blache, Philippe ^a   Van De Wetering, Marc ^b   Duluc, Isabelle ^c   Domon, Claire ^c   Berta, Philippe ^a   Freund, Jean Noël ^c   Clevers, Hans ^b   Jay, Philippe ^a  

^a INSTITUTE OF HUMAN GENETICS   (France)

^b NETHERLANDS CANCER INSTITUTE   (Netherlands)

^c INSERM   (France)

Author keywords

CDX2; Differentiation; Intestinal epithelium; SOX9; Wnt

Indexed keywords

HIGH MOBILITY GROUP PROTEIN; T CELL FACTOR PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR SOX9; UNCLASSIFIED DRUG; WNT PROTEIN;

ANIMAL TISSUE; ARTICLE; CDX2 GENE; CELL LINE; CELL STRAIN HT29; COLON MUCOSA; EPITHELIUM CELL; GENE EXPRESSION SYSTEM; GENE REPRESSION; HOMEOBOX; HOMEOSTASIS; HUMAN; HUMAN CELL; INTESTINE EPITHELIUM; INTESTINE VILLUS; MOUSE; MUC2 GENE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; STEM CELL;

ANIMALS; BETA CATENIN; BLOTTING, NORTHERN; BLOTTING, WESTERN; CARCINOMA; CELL DIFFERENTIATION; CELL LINE, TUMOR; CELL NUCLEUS; COLONIC NEOPLASMS; CYTOSKELETAL PROTEINS; DNA; EPITHELIUM; GENE EXPRESSION REGULATION, NEOPLASTIC; HIGH MOBILITY GROUP PROTEINS; HOMEODOMAIN PROTEINS; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; IMMUNOHISTOCHEMISTRY; INTESTINES; MICE; MICROSCOPY, FLUORESCENCE; MUCINS; NEOPLASM TRANSPLANTATION; PHENOTYPE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA; SIGNAL TRANSDUCTION; STEM CELLS; TRANS-ACTIVATORS; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC; TRANSFECTION;

ANIMALIA;

EID: 3142669010     PISSN: 00219525     EISSN: None     Source Type: Journal    
DOI: 10.1083/jcb.200311021     Document Type: Article

References (73)

1. Akiyama, H., M.C. Chaboissier, J.F. Martin, A. Schedl, and B. de Crombrugghe. 2002. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev. 16:2813-2828.
2. +/- compound mutant mice. Nat. Genet. 35:323-330.
3. Avilion, A.A., S.K. Nicolis, L.H. Pevny, L. Perez, N. Vivian, and R. Lovell-Badge. 2003. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 17:126-140.
4. Batlle, E., J.T. Henderson, H. Beghtel, M.M.W. van den Born, E. Sancho, G. Huls, J. Meeldijk, J. Robertson, M. van de Wetering, T. Pawson, and H. Clevers. 2002. β-Catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/EphrinB. Cell. 111:251-263.
5. Bell, D.M., K.K.H. Leung, S.C. Wheatley, L.J. Ng, S. Zhou, K.W. Ling, M.H. Sham, P. Koopman, P.P.L. Tam, and K.S.E. Cheah. 1997. SOX9 directly regulates the type-II collagen gene. Nat. Genet. 16:174-178.
6. Bi, W., J.M. Deng, Z. Zhang, R.R. Behringer, and B. de Crombrugghe. 1999. Sox9 is required for cartilage formation. Nat. Genet. 22:85-89.
7. Bi, W., W. Huang, D.J. Whitworth, J.M. Deng, Z. Zhang, R.R. Behringer, and B. de Combrugghe. 2001. Haploinsufficiency of Sox9 results in defective cartilage primordia and premature skeletal mineralization. Proc. Natl. Acad. Sci. USA. 98:6698-6703.
8. Bishop, C.E., D.J. Whitworth, Y. Qin, A.I. Agoulnik, W.R. Harrison, R.R. Behringer, and P.A. Overbeek. 2000. A transgenic insertion upstream of Sox9 is associated with dominant XX sex reversal in the mouse. Nat. Genet. 26:490-494.
9. Bonhomme, C., I. Duluc, E. Martin, K. Chawengsaksophak, M.-P. Chenard, M. Kedinger, F. Beck, J.N. Freund, and C. Domon-Dell. 2003. The Cdx2 homeobox gene has a tumour suppressor function in the distal colon, in addition to the homeotic role during gut development. Gut. 52:1465-1471.
10. Brannon, M., M. Gomperts, L. Sumoy, R.T. Moon, and D. Kimelman. 1997. A β-catenin/xTcf3 complex binds to the siamois promoter to regulate dorsal axis specification in xenopus. Genes Dev. 11:2359-2370.
11. Brantjes, H., N. Barker, J. van Es, and H. Clevers. 2002. TCF: Lady Justice casting the final verdict on the outcome of Wnt signalling. Biol. Chem. 383:255-261.
12. Bridgewater, L.C., V. Lefebvre, and B. de Crombrugghe. 1998. Chondrocyte-specific enhancer elements in the Col112a gene resemble the Col2a1 rissue-specific enhancer. J. Biol. Chem. 273:14998-15006.
13. Bylund, M., E. Andersson, B.G. Novitch, and J. Muhr. 2003. Vertebrate neurogenesis is counteracted by Sox1-3 activity. Nat. Neurosci. 6:1162-1168.
14. Cheng, H. 1974. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. II. Mucous cells. Am. J. Anat. 141:481-491.
15. Cheung, M., and J. Briscoe. 2003. Neural crest development is regulated by the transcription factor Sox9. Development. 130:5681-5693.
16. Cremazy, F., S. Soullier, P. Berta, and P. Jay. 1998. Further complexity of the human SOX gene family revealed by the combined use of highly degenerate primers and nested PCR. FEBS Lett. 438:311-314.
17. da Costa, L.T., T.C. He, J. Yu, A.B. Sparks, P.J. Morin, K. Polyak, S. Laken, B. Vogelstein, and K.W. Kinzler. 1999. CDX2 is mutated in a colorectal cancer with normal APC/beta-catenin signaling. Oncogene. 18:5010-5014.
18. de Santa Barbara, P., N. Bonneaud, B. Boizet, M. Desclozeaux, B. Moniot, P. Sudbeck, G. Scherer, F. Poulat, and P. Berta. 1998. Direct interaction of SRY-related protein Sox9 and steroidogenic factor 1 regulates transcription of the human anti-mullerian hormone gene. Mol. Cell. Biol. 18:6653-6665.
19. Duprey, P., K. Chowdhury, G.R. Dressler, R. Balling, D. Simon, J.L. Guenet, and P. Gruss. 1988. A mouse gene homologous to the Drosophila gene caudal is expressed in epithelial cells from the embryonic intestine. Genes Dev. 2:1647-1654.
20. Ee, H., T. Erler, P.S. Bhathal, G.P. Young, and R.J. James. 1995. Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma. Am. J. Pathol. 147:586-592.
21. Fodde, R., W. Edelmann, K. Yang, C. van Leeuwen, C. Carlson, B. Renault, C. Breukel, E. Alt, M. Lipkin, and P.M. Khan. 1994. A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc. Natl. Acad. Sci. USA. 91:8969-8973.
22. Foster, J.M., M.A. Dominguez-Steglich, S. Guioli, C. Kwok, P.A. Weller, M. Stevanovic, J. Weissenbach, S. Mansour, I.D. Young, P.N. Goodfellow, et al. 1994. Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature. 372:525-530.
23. Gottardi, C.J., E. Wong, and B.M. Gumbiner. 2001. E-Cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesion-independent manner. J. Cell Biol. 153:1049-1060.
24. Grotewold, L., and U. Ruther. 2002. Bmp, Fgf and Wnt signalling in programmed cell death and chondrogenesis during vertebrate limb development: the role of Dickkopf-1. Int. J. Dev. Biol. 46:943-947.
25. Harada, N., Y. Tamai, T. Ishikawa, B. Sauer, K. Tabaku, M. Oshima, and M. Taketo. 1999. Intestinal polyposis in mice with a dominant stable mutation of the β-catenin gene. EMBO J. 18:5931-5942.
26. Hartmann, C., and C.J. Tabin. 2000. Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development. 127:3141-3159.
27. He, T.-C., A.B. Sparks, C. Rago, H. Hermeking, L. Zawel, L.T. da Costa, P.J. Morin, B. Vogelstein, and K.W. Kinzler. 1998. Identification of c-MYC as a target of the APC pathway. Science. 281:1509-1512.
28. Hinoi, T., M. Tani, P.C. Lucas, K. Caca, R.L. Dunn, E. Macri, M. Loda, H.D. Appelman, K.R. Cho, and E.R. Fearon. 2001. Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am. J. Pathol. 159:2239-2248.
29. Hinoi, T., M. Loda, and E.R. Fearon. 2003. Silencing of CDX2 expression in colon cancer via a dominant repression pathway. J. Biol. Chem. 278:44608-44616.
30. Ikeya, M., and S. Takada. 2001. Wnt-3a is required for somite specification along the anteroposterior axis of the mouse embryo and for regulation of cdx-1 expression. Mech. Dev. 103:27-33.
31. Kamachi, Y., K.S. Cheah, and H. Kondoh. 1999. Mechanism of regulatory target selection by the SOX high-mobility-group domain proteins as revealed by comparison of SOX1/2/3 and SOX9. Mol. Cell. Biol. 19:107-120.
32. Kamachi, Y., I. Uchikawa, and H. Kondoh. 2000. Pairing SOX off with partners in the regulation of embryonic development. Trends Genet. 16:182-187.
33. Kent, J., S.C. Wheatley, J.E. Andrews, A.H. Sinclair, and P. Koopman. 1996. A male specific role for SOX9 in vertebrate sex determination. Development. 122:2813-2822.
34. Kim, J., L. Lo, E. Dormand, and D.J. Anderson. 2003. SOX10 Maintains multipotency and inhibits neuronal differentiation of neural crest stem cells. Neuron. 38:17-31.
35. Korinek, V., N. Barker, P.J. Morin, D. van Wichen, R. de Weger, K.W. Kinzler, B. Vogelstein, and H. Clevers. 1997. Constitutive transcriptional activation by a β-catenin-Tcf complex in APC-/- colon carcinoma. Science. 275:1784-1787.
36. Korinek, V., N. Barker, P. Moerer, E. van Donselaar, G. Huls, P.J. Peters, and H. Clevers. 1998. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat. Genet. 19:379-383.
37. Kypriotou, M., M. Fossard-Demoor, C. Chadjichristos, C. Ghayor, B. de Crombrugghe, J.P. Pujol, and P. Galera. 2003. SOX9 exerts a bifunctional effect on type II collagen gene (COL2A1) expression in chondrocytes depending on the differentiation state. DATA Cell Biol. 22:119-129.
38. Lefebvre, V., W. Huang, V.R. Harley, P.N. Goodfellow, and B. de Crombrugghe. 1997. SOX9 is a potent activator of the chondrocyte-specific enhancer of the proa1(II) collagen gene. Mol. Cell. Biol. 17:2336-2346.
39. Lickert, H., C. Domon, G. Huls, C. Wehrle, I. Duluc, H. Clevers, B.I. Meyer, J.-N. Freund, and R. Kemler. 2000. Wnt/β-catenin signaling regulates the expression of the homeobox gene Cdx1 in embryonic intestine. Development. 127:3805-3813.
40. Liu, S., R. Guo, and L.D. Quarles. 2001. Cloning and characterization of the proximal murine Phex promoter. Endocrinology. 142:3987-3995.
41. Liu, Y., H. Li, K. Tanaka, N. Tsumaki, and Y. Yamada. 2000. Identification of an enhancer sequence within the first intron required for cartilage-specific transcription of the α2(XI) collagen gene. J. Biol. Chem. 275:12712-12718.
42. Lorentz, O., I. Duluc, A. De Arcangelis, P. Simon-Assmann, M. Kedinger, and J.-N. Freund. 1997. Key role of the Cdx2 homeobox gene in extracellular matrix-mediated intestinal cell differentiation. J. Cell Biol. 139:1553-1565.
43. Lorentz, O., A. Cadoret, I. Duluc, J. Capeau, C. Gespach, G. Cherqui, and J.-N. Freund. 1999. Downregulation of the colon tumour-suppressor homeobox gene Cdx-2 by oncogenic ras. Oncogene. 18:87-92.
44. Mallo, G.V., H. Rechreche, J.-M. Frigerio, D. Rocha, A. Zweibaum, M. Lacasa, B.R. Jordan, N.J. Dusetti, J.-C. Dagorn, and J.L. Iovanna. 1997. Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and CDX2 homeobox, down-regulation of Cdx1 and Cdx2 expression during colorectal carcinogenesis. Int. J. Cancer. 74:35-44.
45. Mori-Akiyama, Y., H. Akiyama, D.H. Rowitch, and B. De Crombrugghe. 2003. Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest. Proc. Natl. Acad. Sci. USA. 100:9360-9365.
46. Morin, P.J., A.B. Sparks, V. Korinek, N. Barker, H. Clevers, B. Vogelstein, and K.W. Kinzler. 1997. Activation of β-catenin-Tcf signaling in colon cancer by mutations in β-catenin or APC. Science. 275:1787-1790.
47. Ng, L.-J., S. Wheatley, G.E.O. Muscat, J. Conway-Campbell, J. Bowles, E. Wright, D.M. Bell, P.P.L. Tam, K.S.E. Cheah, and P. Koopman. 1997. SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev. Biol. 183:108-121.
48. Panda, D.K., D. Miao, V. Lefebvre, G.N. Hendy, and D. Golzman. 2001. The transcription factor SOX9 regulates cell cycle and differentiation genes in chondrogenic CFK2 cells. J. Biol. Chem. 276:41229-41236.
49. Pinto, D., A. Gregorieff, H. Begthel, and H. Clevers. 2003. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev. 17:1709-1713.
50. Potten, C.S., and M. Moeffler. 1990. Stem cells: attributes, cycles, pitfalls and uncertainties lessons for and from the crypt. Development. 110:1001-1020.
51. Rings, E.H.H.M., F. Boudreau, J.K. Taylor, J. Moffett, E.R. Suh, and P.G. Traber. 2001. Phsphorylation of the serine 60 residue within the Cdx2 activation domain mediates its transactivation capacity. Gastroenterology. 121:1437-1450.
52. Sekiya, I., K. Tsuji, P. Koopman, H. Watanabe, Y. Yamada, K. Shinomiya, A. Nifuji, and M. Noda. 2000. SOX9 enhances aggrecan gene promoter/enhancer activity and is up-regulated by retinoic acid in a cartilage-derived cell line, TC6. J. Biol. Chem. 275:10738-10744.
53. Shibata, H., K. Toyama, H. Shioya, M. Ito, M. Hirota, S. Hasegawa, H. Matsumoto, H. Takano, T. Akiyama, K. Toyoshima, et al. 1997. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science. 278:120-123.
54. Silberg, D.G., G.P. Swain, E.R. Suh, and P.G. Traber. 2000. Cdx1 and Cdx2 expression during intestinal development. Gastroenterology. 119:961-971.
55. Simcha, I., C. Kirkpatrick, E. Sadot, M. Shtutman, G. Polevoy, B. Geiger, M. Peifer, and A. Ben-Ze'ev. 2001. Cadherin sequences that inhibit beta-catenin signaling: a study in yeast and mammalian cells. Mol. Biol. Cell. 12:1177-1188.
56. Smith, J.M., and P.A. Koopman. 2004. The ins and outs of transcriptional control: nucleocytoplasmic shuttling in development and disease. Trends Genet. 20:4-8.
57. Spokony, R.F., Y. Aoki, N. Saint-Germain, E. Magner-Fink, and J.P. Saint-Jeannet. 2002. The transcription factor Sox9 is required for cranial neural crest development in Xenopus. Development. 129:421-432.
58. Stappenbeck, T.S., M.H. Wong, J.R. Saam, I.U. Mysorekar, and J.I. Gordon. 1998. Notes from some crypt watchers: regulation of renewal in the mouse intestinal epithelium. Curr. Opin. Cell Biol. 10:702-709.
59. Stolt, C.C., S. Rehberg, M. Ader, P. Lommes, D. Riethmacher, M. Schachner, U. Bartsch, and M. Wegner. 2002. Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10. Genes Dev. 16:165-170.
60. Stolt, C.C., P. Lommes, E. Sock, M.C. Chaboissier, A. Schedl, and M. Wegner. 2003. The Sox9 transcription factor determines glial fate choice in the developing spinal cord. Genes Dev. 17:1677-1689.
61. Subramanian, V., B. Meyer, and G.S. Evans. 1998. The murine Cdx1 gene product localises to the proliferative compartment in the developing and regenerating intestinal epithelium. Differentiation. 64:11-18.
62. Südbeck, P., L. Schmitz, P.A. Baeuerle, and G. Scherer. 1996. Sex reversal by loss of the C-terminal transactivation domain of human SOX9. Nat. Genet. 13:230-232.
63. Suh, E., L. Chen, J. Taylor, and P.G. Traber. 1994. A homeodomain protein related to caudal regulates intestine-specific gene transcription. Mol. Cell. Biol. 14:7340-7351.
64. Tetsu, O., and F. McCormick. 1999. β-Catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 398:422-426.
65. van de Wetering, M., E. Sancho, C. Verweij, W. de Lau, I. Oving, A. Hurlstone, K. van der Horn, E. Batlle, D. Coudreuse, A.P. Haramis, et al. 2002. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 111:241-250.
66. Velcich, A., W.C. Yang, J. Heyer, A. Fragale, C. Nicholas, S. Viani, R. Kucherlapati, M. Lipkin, K. Yang, and L. Augenlicht. 2002. Colorectal cancer in mice genetically deficient in the Mucin Muc2. Science. 295:1726-1729.
67. Wagner, T., J. Wirth, J. Meyer, B. Zabel, M. Held, J. Zimmer, J. Pasantes, F.D. Bricarelli, J. Keutel, E. Hustert, et al. 1994. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell. 79:1111-1120.
68. Willert, J., M. Epping, J.R. Pollack, P.O. Brown, and R. Nusse. 2002. A transcriptional response to Wnt protein in human embryonic carcinoma cells. BMC Dev. Biol. 2:8.
69. Wright, E., M.R. Hargrave, J. Christiansen, L. Cooper, J. Kun, T. Evans, U. Gandadharan, A. Greenfield, and P. Koopman. 1995. The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos. Nat. Genet. 9:15-20.
70. Wunderle, V.M., R. Critcher, N. Hastie, P.N. Goodfellow, and A. Schedl. 1998. Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia. Proc. Natl. Acad. Sci. USA. 95:10649-10654.
71. Xie, W.F., X. Zhang, S. Sakano, V. Lefebvre, and L.J. Sandell. 1999. Trans-activation of the mouse cartilage-derived retinoic acid-sensitive protein gene by Sox9. J. Bone Miner. Res. 14:757-763.
72. Yamamoto, H., Y.Q. Bai, and Y. Yuasa. 2003. Homeodomain protein CDX2 regulates goblet-specific MUC2 gene expression. Biochem. Biophys. Res. Commun. 300:813-818.
73. Yanfeng, W., J.P. Saint-Jeannet, and P.S. Klein. 2003. Wnt-frizzled signaling in the induction and differentiation of the neural crest. Bioessays. 25:317-325.