Cdx1 promotes differentiation in a rat intestinal epithelial cell line.
OBJECTIVE
Homeobox genes are involved in establishing and maintaining differentiated patterns in adult tissues. Cdx1 might carry out that function in the intestinal epithelium because its expression is specific to that tissue and increases during development.


METHODS
Cdx1 expression was induced in IEC-6 intestinal epithelial cells by stable transfection, and subsequent changes in cell growth, resistance to apoptosis, migration, and differentiation were monitored.


RESULTS
Compared with control, IEC-6/Cdx1 cells proliferated more rapidly, were more resistant to apoptosis, and migrated 3-4 times faster, as shown by an in vitro wound assay. IEC-6/Cdx1 cells in culture formed multilayers. Morphology of the top layer was similar to that of columnar epithelium, with cells showing typical features of differentiated enterocytes, including complex junctions and well-developed microvilli with glycocalix. Expression of 2 markers of enterocyte differentiation, aminopeptidase N and villin, was induced in IEC-6/Cdx1 cells. Aminopeptidase N was targeted to the basolateral membrane, and villin was localized to the cytoplasm. Actin filaments, which were mostly present in transcytoplasmic stress fibers in control cells, were redistributed to the cortex in Cdx1-transfected cells.


CONCLUSIONS
Cdx1 expression in IEC-6 cells induces phenotypic changes characteristic of differentiating enterocytes, suggesting an important role for Cdx1 in the transition from stem cells to proliferating/transit cells.
Soubeyran
P
P
INSERM Unité 315, Laboratoire de Physiologie et Pathologie Digestives, Marseille, France.
André
F
F
Lissitzky
J C
JC
Mallo
G V
GV
Moucadel
V
V
Roccabianca
M
M
Rechreche
H
H
Marvaldi
J
J
Dikic
I
I
Dagorn
J C
JC
Iovanna
J L
JL
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D030161:Avian Proteins; D018826:CD13 Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology*; D008840:Microfilament Proteins / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D013234:Stem Cells / Q000166:cytology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000199:Actins; D030161:Avian Proteins; D002352:Carrier Proteins; C491271:Cdx1 protein, rat; D018398:Homeodomain Proteins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; C026615:villin; D018826:CD13 Antigens