GATA factors regulate proliferation, differentiation, and gene expression in small intestine of mature mice.
OBJECTIVE
GATA transcription factors regulate proliferation, differentiation, and gene expression in multiple organs. GATA4 is expressed in the proximal 85% of the small intestine and regulates the jejunal-ileal gradient in absorptive enterocyte gene expression. GATA6 is co-expressed with GATA4 but also is expressed in the ileum; its function in the mature small intestine is unknown.


METHODS
We investigated the function of GATA6 in small intestine using adult mice with conditional, inducible deletion of Gata6, or Gata6 and Gata4, specifically in the intestine.


RESULTS
In ileum, deletion of Gata6 caused a decrease in crypt cell proliferation and numbers of enteroendocrine and Paneth cells, an increase in numbers of goblet-like cells in crypts, and altered expression of genes specific to absorptive enterocytes. In contrast to ileum, deletion of Gata6 caused an increase in numbers of Paneth cells in jejunum and ileum. Deletion of Gata6 and Gata4 resulted in a jejunal and duodenal phenotype that was nearly identical to that in the ileum after deletion of Gata6 alone, revealing common functions for GATA6 and GATA4.


CONCLUSIONS
GATA transcription factors are required for crypt cell proliferation, secretory cell differentiation, and absorptive enterocyte gene expression in the small intestinal epithelium.
Division of Gastroenterology and Nutrition, Department of Medicine, Children's Hospital Boston, Boston, Massachusetts, USA.
Eva
E
Beuling
Nana Yaa A
NY
Baffour-Awuah
Kelly A
KA
Stapleton
Boaz E
BE
Aronson
Taeko K
TK
Noah
Noah F
NF
Shroyer
Stephen A
SA
Duncan
James C
JC
Fleet
Stephen D
SD
Krasinski
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004386:Duodenum / Q000166:cytology / Q000502:physiology; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D050991:GATA4 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D050993:GATA6 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D007082:Ileum / Q000166:cytology / Q000502:physiology; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology; D007421:Intestine, Small / Q000166:cytology / Q000502:physiology*; D007583:Jejunum / Q000166:cytology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D019879:Paneth Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism
D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; C484171:Gata4 protein, mouse; C494760:Gata6 protein, mouse; D051880:Receptors, Notch; D051153:Wnt Proteins
J Biol Chem. 2004 Mar 26;279(13):12876-82
14709552
Blood. 2002 Nov 15;100(10):3512-20
12393444
Dev Biol. 2008 Dec 15;324(2):288-96
18948094
BMC Dev Biol. 2006 Apr 12;6:19
16611361
Cell. 2002 Oct 18;111(2):241-50
12408868
Exp Cell Res. 2010 Feb 1;316(3):452-65
19786015
Gastroenterology. 2004 May;126(5):1236-46
15131783
Nat Genet. 1998 Aug;19(4):379-83
9697701
Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):266-71
14695885
J Biol Chem. 2000 Dec 15;275(50):38949-52
11042222
EMBO J. 2002 Dec 2;21(23):6338-47
12456641
Nature. 2005 Jun 16;435(7044):959-63
15959515
Science. 2001 Dec 7;294(5549):2155-8
11739954
Nat Cell Biol. 2005 Apr;7(4):381-6
15778706
EMBO Rep. 2008 Apr;9(4):377-83
18274550
Gastroenterology. 2008 Nov;135(5):1676-1686.e1
18812176
Cell. 2002 Oct 18;111(2):251-63
12408869
J Biol Chem. 1998 May 29;273(22):13713-8
9593712
Oncogene. 2009 Aug 27;28(34):3033-46
19543315
Gut. 2010 Jul;59(7):888-95
20581237
Mol Cell Biol. 2006 Dec;26(23):9060-70
16940177
BMC Gastroenterol. 2008 Apr 11;8:9
18405344
Am J Physiol Gastrointest Liver Physiol. 2007 May;292(5):G1302-14
17272516
Genesis. 2004 Jul;39(3):186-93
15282745
Curr Opin Cell Biol. 1998 Dec;10(6):702-9
9914172
Mol Cell Biol. 2003 Jul;23(14):5031-42
12832487
Development. 2005 Mar;132(5):1093-104
15689380
Annu Rev Physiol. 2009;71:241-60
18808327
Am J Physiol Gastrointest Liver Physiol. 2004 Oct;287(4):G899-909
15178553
Genes Dev. 2003 Jul 15;17(14):1709-13
12865297
Am J Physiol Gastrointest Liver Physiol. 2004 Nov;287(5):G1086-99
14715527
J Cell Biol. 2007 Aug 13;178(4):635-48
17698607
Gastroenterology. 2009 Oct;137(4):1333-45.e1-3
19549527
Development. 2005 Mar;132(6):1443-51
15716339
Gastroenterology. 2007 Aug;133(2):539-46
17681175
Genes Dev. 2005 Oct 15;19(20):2412-7
16230531
Dev Biol. 2008 Oct 1;322(1):179-89
18692040
Nature. 2005 Jun 16;435(7044):964-8
15959516
J Cell Biol. 1989 Dec;109(6 Pt 2):3231-42
2689454
Nat Genet. 2000 Jan;24(1):36-44
10615124
Mol Cell Biol. 2008 Sep;28(17):5420-31
18591257