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PMID: 12015290 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon.

Development (Cambridge, England) ·Vol. 129 ·No. 11 ·2002-06-00 ·Pages 2619-28

Katz JP, Perreault N, Goldstein BG, Lee CS, Labosky PA, Yang VW, Kaestner KH

Abstract

Klf4 (formerly GKLF) is a zinc-finger transcription factor expressed in the epithelia of the skin, lungs, gastrointestinal tract and several other organs. In vitro studies have suggested that Klf4 plays an important role in cell proliferation and/or differentiation. Mice homozygous for a null mutation in Klf4 die within 15 hours of birth and show selective perturbation of late-stage differentiation structures in the epidermis, but the function of Klf4 in the gastrointestinal tract has not been investigated. To address this issue, we have generated Klf4(-/-) mice by homologous recombination in embryonic stem cells. In this study, we provide the first in vivo evidence that Klf4 is a goblet cell-specific differentiation factor in the colon. Klf4(-/-) mice exhibit normal cell proliferation and cell death rates in the colon on postnatal day 1. However, Klf4(-/-) mice demonstrate a 90% decrease in the number of goblet cells in the colon, show abnormal expression of the goblet cell-specific marker Muc2 by in situ hybridization, have abnormal staining of the colonic epithelium with Alcian Blue for acidic mucins, and lack normal goblet cell morphology by ultrastructural analysis. All other epithelial cell types are present in the colon of Klf4(-/-) mice. In summary, Klf4 plays a crucial role in colonic epithelial cell differentiation in vivo.

MeSH Terms
Animals Base Sequence Cell Death Cell Differentiation/physiology Cell Division Colon DNA-Binding Proteins/deficiency,genetics,metabolism Exons Genotype Goblet Cells/cytology,ultrastructure Intestinal Mucosa/cytology Kruppel-Like Factor 4 Kruppel-Like Transcription Factors Mice Mice, Knockout Polymerase Chain Reaction Restriction Mapping Transcription Factors/deficiency,genetics,metabolism Zinc Fingers
Chemicals
DNA-Binding Proteins Klf4 protein, mouse Kruppel-Like Factor 4 Kruppel-Like Transcription Factors Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Katz Jonathan P
Department of Genetics, University of Pennsylvania School of Medicine, 560 Clinical Research Building, 415 Curie Blvd, Philadelphia 19104-6145, USA.
Perreault Nathalie
Goldstein Bree G
Lee Catherine S
Labosky Patricia A
Yang Vincent W
Kaestner Klaus H
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
0950-1991
Published
2002-06-00
Pages
2619-28
Language
English
Region
England
NLM ID
8701744
PMCID
PMC2225535
Subset
IM
Grants
NIDDK NIH HHS · R01 DK53839 · United States
NIDDK NIH HHS · R01 DK052230 · United States
NIDDK NIH HHS · K08 DK02809-01 · United States
NIDDK NIH HHS · R01 DK052230-04 · United States
NIDDK NIH HHS · P30 DK050306 · United States
NCI NIH HHS · R01 CA084197 · United States
NIDDK NIH HHS · R01 DK52230 · United States
NIDDK NIH HHS · P30 DK50306 · United States
NIDDK NIH HHS · R01 DK053839 · United States
NCI NIH HHS · R01 CA84197 · United States
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PubMed source PMC Full Text View journal details
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