Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine

Stephanie Grainger, Alexa Kathryn Hryniuk, David Lohnes

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The caudal-related homeodomain transcription factors Cdx1 and Cdx2 are expressed in the developing endoderm with expression persisting into adulthood. Cdx1-/- mutants are viable and fertile and display no overt intestinal phenotype. Cdx2 null mutants are peri-implantation lethal; however, conditional mutation approaches have revealed that Cdx2 is required for patterning the intestinal epithelium and specification of the colon. Cdx2 is also necessary for homeostasis of the intestinal tract in the adult, where Cdx1 and Cdx2 appear to functionally overlap in the distal colon, but not during intestinal development. Cdx1 and Cdx2 exhibit complete overlap of expression in the intestine, although they differ in their relative levels, with Cdx1 maximal in the distal colon and Cdx2 peaking in the proximal cecum. Moreover, Cdx1 protein is graded along the crypt-villus axis, being abundant in the crypts and diminishing towards the villi. Cdx2 is expressed uniformly along this axis, but is differentially phosphorylated; the functional relevance of these expression domains and phosphorylation is currently unknown. Cdx1 and Cdx2 have been suggested to exhibit functional specificity in the intestinal tract. In the present study, using cell-based models, we found that relative to Cdx1, Cdx2 was significantly less potent at effecting a transcriptional response from the Cdx1 promoter, a known Cdx target gene. We subsequently assessed this relationship in vivo using a "gene swap" approach and found that Cdx2 cannot substitute for Cdx1 in this autoregulatory loop. This is in marked contrast with the ability of Cdx2 to support Cdx1 expression and function in paraxial mesoderm and vertebral patterning, thus providing novel in vivo evidence of context-dependent transcriptional specificity between these transcription factors.

Original languageEnglish (US)
Article numbere54757
JournalPloS one
Volume8
Issue number1
DOIs
StatePublished - Jan 30 2013
Externally publishedYes

Fingerprint

colon
Intestines
Colon
intestines
Transcription Factors
Genes
villi
Phosphorylation
transcription factors
mutants
Endoderm
Cecum
Mesoderm
Intestinal Mucosa
intestinal mucosa
adulthood
Specifications
lethal genes
cecum
homeostasis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine. / Grainger, Stephanie; Hryniuk, Alexa Kathryn; Lohnes, David.

In: PloS one, Vol. 8, No. 1, e54757, 30.01.2013.

Research output: Contribution to journalArticle

Grainger, Stephanie ; Hryniuk, Alexa Kathryn ; Lohnes, David. / Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine. In: PloS one. 2013 ; Vol. 8, No. 1.
@article{813f62bff8864c38bc30b3f46a0a77cf,
title = "Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine",
abstract = "The caudal-related homeodomain transcription factors Cdx1 and Cdx2 are expressed in the developing endoderm with expression persisting into adulthood. Cdx1-/- mutants are viable and fertile and display no overt intestinal phenotype. Cdx2 null mutants are peri-implantation lethal; however, conditional mutation approaches have revealed that Cdx2 is required for patterning the intestinal epithelium and specification of the colon. Cdx2 is also necessary for homeostasis of the intestinal tract in the adult, where Cdx1 and Cdx2 appear to functionally overlap in the distal colon, but not during intestinal development. Cdx1 and Cdx2 exhibit complete overlap of expression in the intestine, although they differ in their relative levels, with Cdx1 maximal in the distal colon and Cdx2 peaking in the proximal cecum. Moreover, Cdx1 protein is graded along the crypt-villus axis, being abundant in the crypts and diminishing towards the villi. Cdx2 is expressed uniformly along this axis, but is differentially phosphorylated; the functional relevance of these expression domains and phosphorylation is currently unknown. Cdx1 and Cdx2 have been suggested to exhibit functional specificity in the intestinal tract. In the present study, using cell-based models, we found that relative to Cdx1, Cdx2 was significantly less potent at effecting a transcriptional response from the Cdx1 promoter, a known Cdx target gene. We subsequently assessed this relationship in vivo using a {"}gene swap{"} approach and found that Cdx2 cannot substitute for Cdx1 in this autoregulatory loop. This is in marked contrast with the ability of Cdx2 to support Cdx1 expression and function in paraxial mesoderm and vertebral patterning, thus providing novel in vivo evidence of context-dependent transcriptional specificity between these transcription factors.",
author = "Stephanie Grainger and Hryniuk, {Alexa Kathryn} and David Lohnes",
year = "2013",
month = "1",
day = "30",
doi = "10.1371/journal.pone.0054757",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine

AU - Grainger, Stephanie

AU - Hryniuk, Alexa Kathryn

AU - Lohnes, David

PY - 2013/1/30

Y1 - 2013/1/30

N2 - The caudal-related homeodomain transcription factors Cdx1 and Cdx2 are expressed in the developing endoderm with expression persisting into adulthood. Cdx1-/- mutants are viable and fertile and display no overt intestinal phenotype. Cdx2 null mutants are peri-implantation lethal; however, conditional mutation approaches have revealed that Cdx2 is required for patterning the intestinal epithelium and specification of the colon. Cdx2 is also necessary for homeostasis of the intestinal tract in the adult, where Cdx1 and Cdx2 appear to functionally overlap in the distal colon, but not during intestinal development. Cdx1 and Cdx2 exhibit complete overlap of expression in the intestine, although they differ in their relative levels, with Cdx1 maximal in the distal colon and Cdx2 peaking in the proximal cecum. Moreover, Cdx1 protein is graded along the crypt-villus axis, being abundant in the crypts and diminishing towards the villi. Cdx2 is expressed uniformly along this axis, but is differentially phosphorylated; the functional relevance of these expression domains and phosphorylation is currently unknown. Cdx1 and Cdx2 have been suggested to exhibit functional specificity in the intestinal tract. In the present study, using cell-based models, we found that relative to Cdx1, Cdx2 was significantly less potent at effecting a transcriptional response from the Cdx1 promoter, a known Cdx target gene. We subsequently assessed this relationship in vivo using a "gene swap" approach and found that Cdx2 cannot substitute for Cdx1 in this autoregulatory loop. This is in marked contrast with the ability of Cdx2 to support Cdx1 expression and function in paraxial mesoderm and vertebral patterning, thus providing novel in vivo evidence of context-dependent transcriptional specificity between these transcription factors.

AB - The caudal-related homeodomain transcription factors Cdx1 and Cdx2 are expressed in the developing endoderm with expression persisting into adulthood. Cdx1-/- mutants are viable and fertile and display no overt intestinal phenotype. Cdx2 null mutants are peri-implantation lethal; however, conditional mutation approaches have revealed that Cdx2 is required for patterning the intestinal epithelium and specification of the colon. Cdx2 is also necessary for homeostasis of the intestinal tract in the adult, where Cdx1 and Cdx2 appear to functionally overlap in the distal colon, but not during intestinal development. Cdx1 and Cdx2 exhibit complete overlap of expression in the intestine, although they differ in their relative levels, with Cdx1 maximal in the distal colon and Cdx2 peaking in the proximal cecum. Moreover, Cdx1 protein is graded along the crypt-villus axis, being abundant in the crypts and diminishing towards the villi. Cdx2 is expressed uniformly along this axis, but is differentially phosphorylated; the functional relevance of these expression domains and phosphorylation is currently unknown. Cdx1 and Cdx2 have been suggested to exhibit functional specificity in the intestinal tract. In the present study, using cell-based models, we found that relative to Cdx1, Cdx2 was significantly less potent at effecting a transcriptional response from the Cdx1 promoter, a known Cdx target gene. We subsequently assessed this relationship in vivo using a "gene swap" approach and found that Cdx2 cannot substitute for Cdx1 in this autoregulatory loop. This is in marked contrast with the ability of Cdx2 to support Cdx1 expression and function in paraxial mesoderm and vertebral patterning, thus providing novel in vivo evidence of context-dependent transcriptional specificity between these transcription factors.

UR - http://www.scopus.com/inward/record.url?scp=84873851409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873851409&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0054757

DO - 10.1371/journal.pone.0054757

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e54757

ER -