Transcriptional modulation of genes encoding structural characteristics of differentiating enterocytes during development of a polarized epithelium in vitro.
Although there is considerable evidence implicating posttranslational mechanisms in the development of epithelial cell polarity, little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized the temporal program of gene expression during cell-cell adhesion-initiated polarization of human Caco-2 cells in tissue culture, which develop structural and functional polarity similar to that of enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell-cell contacts between neighboring cells. Expression of genes involved in cell proliferation was down-regulated concomitant with induction of genes necessary for functional specialization of polarized epithelial cells. Transcriptional up-regulation of these latter genes correlated with formation of important structural and functional features in enterocyte differentiation and establishment of structural and functional cell polarity; components of the apical microvilli were induced as the brush border formed during polarization; as barrier function was established, expression of tight junction transmembrane proteins peaked; transcripts encoding components of the apical, but not the basal-lateral trafficking machinery were increased during polarization. Coordinated expression of genes encoding components of functional cell structures were often observed indicating temporal control of expression and assembly of multiprotein complexes.
Halbleib
Jennifer M
JM
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
Sääf
Annika M
AM
Brown
Patrick O
PO
Nelson
W James
WJ
D000199:Actins / Q000378:metabolism; D018938:Caco-2 Cells; D002448:Cell Adhesion; D002454:Cell Differentiation; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism; D020895:Enterocytes / Q000166:cytology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D014158:Transcription, Genetic / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D000199:Actins; C448939:CRB1 protein, human; D005136:Eye Proteins; C407989:JTB protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; D020741:rho GTP-Binding Proteins
Nat Rev Mol Cell Biol. 2001 Feb;2(2):107-17
11252952
J Biol Chem. 2004 Dec 31;279(53):55506-13
15507455
Cancer Res. 2002 Sep 15;62(18):5351-7
12235006
Semin Cell Dev Biol. 2004 Dec;15(6):643-56
15561584
Mol Biol Cell. 2007 Nov;18(11):4245-60
17699589
J Cell Biol. 2004 Sep 27;166(7):1093-102
15452149
Cancer Metastasis Rev. 1996 Dec;15(4):507-25
9034607
Mol Membr Biol. 2003 Apr-Jun;20(2):129-39
12851070
Proc Natl Acad Sci U S A. 1978 Oct;75(10):5034-8
368806
J Cell Biol. 1998 Jul 13;142(1):101-15
9660866
J Cell Biol. 2001 Oct 1;155(1):77-88
11581287
Cancer Res. 1988 Apr 1;48(7):1936-42
3349466
J Cell Biol. 2003 Feb 3;160(3):423-32
12566432
Biochem J. 2006 Jul 1;397(1):1-14
16761954
J Cell Biol. 2001 Apr 16;153(2):263-72
11309408
Novartis Found Symp. 2005;269:144-55; discussion 155-8, 223-30
16355539
Am J Physiol Gastrointest Liver Physiol. 2002 Sep;283(3):G496-502
12181160
Int Rev Cytol. 2006;248:261-98
16487793
Cancer Sci. 2003 Jun;94(6):501-7
12824874
FEBS Lett. 2000 Jun 30;476(1-2):32-7
10878245
Nat Cell Biol. 2004 Dec;6(12):1180-8
15558031
Curr Opin Genet Dev. 2003 Aug;13(4):341-50
12888006
Nat Rev Mol Cell Biol. 2005 Mar;6(3):233-47
15738988
Curr Opin Cell Biol. 2003 Oct;15(5):572-82
14519392
Trends Biochem Sci. 1995 May;20(5):187-90
7610482
Cell. 2003 Jul 25;114(2):229-39
12887924
Nat Rev Cancer. 2006 Apr;6(4):307-20
16557282
Nat Rev Mol Cell Biol. 2005 Feb;6(2):167-80
15688002
Trends Cell Biol. 1999 Nov;9(11):423-7
10511705
Biochim Biophys Acta. 2004 Mar 23;1662(1-2):3-21
15033576
EMBO J. 1998 Apr 1;17(7):1919-29
9524115
Curr Opin Gastroenterol. 2006 Mar;22(2):85-9
16462161
Curr Opin Cell Biol. 2002 Aug;14(4):417-22
12383791
Curr Biol. 2001 Oct 30;11(21):R858-61
11696341
Curr Opin Cell Biol. 1995 Oct;7(5):650-7
8573339
Differentiation. 1993 Jun;53(2):95-104
7689500
Am J Physiol. 1985 May;248(5 Pt 1):C410-8
2986462
J Biol Chem. 1998 Nov 13;273(46):30263-70
9804786
Curr Opin Cell Biol. 2003 Aug;15(4):405-13
12892780
EMBO J. 2001 Aug 1;20(15):4076-87
11483511
Cell. 2005 Dec 2;123(5):769-72
16325573
J Biol Chem. 1990 Feb 25;265(6):3503-12
1968064
J Cell Biol. 1996 Apr;133(2):417-30
8609173
Cell. 2003 Feb 21;112(4):453-65
12600310
Physiol Rev. 1999 Jan;79(1):73-98
9922368
Melanoma Res. 1993 Feb;3(1):35-41
8471835
Exp Cell Res. 2005 Jun 10;306(2):357-63
15925592
Genomics. 2001 Mar 15;72(3):285-96
11401444
Annu Rev Physiol. 2006;68:403-29
16460278
Nat Genet. 1997 Sep;17(1):32-9
9288095
Nature. 2003 Apr 17;422(6933):766-74
12700771
J Cell Biol. 2001 Nov 12;155(4):593-604
11696560
Mol Cell Biochem. 2003 Jan;242(1-2):35-8
12619863
Nat Rev Mol Cell Biol. 2005 Aug;6(8):622-34
16025097
Mech Dev. 2001 Mar;101(1-2):3-9
11231054
J Cell Biol. 2002 Jul 22;158(2):293-303
12135985
J Biol Chem. 2002 May 3;277(18):16332-9
11872745
J Cell Biol. 1987 Sep;105(3):1283-96
2888771
Cell. 1990 Feb 9;60(3):429-37
2302734
J Cell Sci. 1995 Jan;108 ( Pt 1):369-77
7738111
Curr Opin Cell Biol. 1992 Feb;4(1):27-35
1558751
J Histochem Cytochem. 1996 Nov;44(11):1267-77
8918902
J Cell Biol. 2005 May 9;169(3):491-501
15883199
Int J Cancer. 2005 Sep 1;116(3):351-8
15800939
J Mol Biol. 1977 Sep 25;115(3):465-83
563468
Nat Cell Biol. 2004 Dec;6(12):1173-9
15558032
Nat Cell Biol. 2003 Feb;5(2):126-36
12545172
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9313-7
2687880
Curr Opin Cell Biol. 1999 Feb;11(1):45-53
10047518
Exp Cell Res. 2005 Feb 15;303(2):494-503
15652360
Curr Opin Cell Biol. 2003 Feb;15(1):67-72
12517706
Science. 2004 Mar 5;303(5663):1483-7
15001769
J Cell Biol. 2004 Mar 29;164(7):1009-20
15037601
Curr Opin Gastroenterol. 2003 Nov;19(6):583-90
15703609
Physiol Rev. 2003 Oct;83(4):1359-400
14506308
Oncogene. 2000 Jan 20;19(3):380-6
10656685
Cell. 2002 Sep 20;110(6):673-87
12297042
Curr Biol. 1999 Jul 15;9(14):R515-7
10421564
Dev Cell. 2002 Aug;3(2):259-70
12194856
Dev Dyn. 1996 May;206(1):12-23
9019243
Nat Rev Mol Cell Biol. 2006 May;7(5):347-58
16633337
J Cell Sci. 2001 Oct;114(Pt 20):3583-90
11707510
Mol Biol Cell. 2004 Jan;15(1):91-8
14565974
Nat Rev Mol Cell Biol. 2004 Apr;5(4):271-81
15071552
Genes Dev. 2004 Aug 15;18(16):1909-25
15314019
Proc Natl Acad Sci U S A. 2001 May 22;98(11):6174-9
11371639
Ann N Y Acad Sci. 1998 Nov 17;859:46-64
9928369
Nat Cell Biol. 2003 Jan;5(1):53-8
12510194
Nat Rev Mol Cell Biol. 2004 Aug;5(8):614-25
15366705
J Cell Biol. 1990 Oct;111(4):1351-61
1976637
Cell. 2007 Jan 26;128(2):383-97
17254974
J Cell Biol. 1989 Dec;109(6 Pt 1):2817-32
2592406
Mol Cell Biol. 2005 May;25(9):3726-36
15831477
J Cell Biol. 1990 May;110(5):1533-9
2335561
Exp Cell Res. 2004 Aug 15;298(2):388-98
15265687
Annu Rev Cell Dev Biol. 2004;20:811-38
15473861
Nature. 2000 Oct 26;407(6807):1022-6
11069184
Curr Opin Cell Biol. 2002 Oct;14(5):537-45
12231347
Annu Rev Cell Biol. 1985;1:209-41
3916317
J Biol Chem. 1985 Jan 10;260(1):139-46
3965444
Cell. 1994 Mar 25;76(6):1053-61
8137422
EMBO J. 1990 Oct;9(10):3163-70
2209541
Cancer Res. 1995 Jul 15;55(14):2972-7
7606712
FEBS Lett. 2005 Oct 10;579(24):5253-9
16182290
J Cell Sci. 1997 Dec;110 ( Pt 24):3055-64
9365275
J Cell Sci. 2004 Mar 1;117(Pt 7):1091-104
14970258
J Cell Biol. 2000 May 15;149(4):761-6
10811817
J Cell Biol. 1996 Apr;133(2):247-56
8609159
Am J Physiol Renal Physiol. 2003 Sep;285(3):F377-87
12890661
Nat Rev Mol Cell Biol. 2002 Jul;3(7):531-7
12094219
J Cell Biol. 1982 Oct;95(1):105-17
7142282
Am J Physiol Cell Physiol. 2003 Jun;284(6):C1346-54
12700140
Nat Rev Mol Cell Biol. 2001 Feb;2(2):98-106
11252968
Trends Cell Biol. 2005 Apr;15(4):222-8
15817379
J Cell Biol. 1989 Dec;109(6 Pt 2):3391-401
2557354
Curr Biol. 2006 Feb 21;16(4):408-14
16488876
Semin Cancer Biol. 2005 Oct;15(5):342-52
15963732
J Cell Biol. 1991 Apr;113(2):275-88
1672691
Annu Rev Cell Dev Biol. 2005;21:247-69
16212495
Int J Biochem Cell Biol. 2002 Jul;34(7):713-7
11950587
Br J Cancer. 1999 Jan;79(2):211-3
9888459
Nat Cell Biol. 2003 Jan;5(1):46-52
12510193
J Cell Biol. 2005 Jan 17;168(2):281-90
15657398
Bioessays. 2002 Apr;24(4):350-61
11948621
Cancer Res. 2006 Jan 1;66(1):2-5
16397205
Am J Physiol. 1999 Aug;277(2 Pt 2):F277-89
10444583
Oncology (Williston Park). 2006 May;20(6):579-87; discussion 588, 594, 596 passim
16773844
Cell Struct Funct. 2005 Feb;29(5-6):147-57
15840946
Mol Cell Biol. 2006 Mar;26(6):2387-98
16508013