Inactivation of the transcription factor Elf3 in mice results in dysmorphogenesis and altered differentiation of intestinal epithelium.
OBJECTIVE
The mammalian small intestine is lined by a highly specialized epithelium that functions in the digestion and absorption of nutrients. The molecular mechanisms that direct intestinal epithelial cell morphogenesis and terminal differentiation are poorly understood. We have previously identified Elf3 (E74-like factor-3) as a member of the ETS transcription factor family strongly expressed in small intestinal epithelium. The aim of this study is to investigate the biological roles of Elf3 in vivo.


METHODS
Mice with a null mutation of Elf3 were generated through targeted gene disruption. Characterization of intestinal development was performed by histologic and immunohistochemical techniques.


RESULTS
Targeted disruption of Elf3 resulted in fetal lethality of about 30% at around embryonic day 11.5. Seventy percent of the Elf3-deficent progeny were born and displayed severe alterations of tissue architecture in the small intestine, manifested by poor villus formation and abnormal morphogenesis and terminal differentiation of absorptive enterocytes and mucus-secreting goblet cells. Crypt cell proliferation, however, appeared intact in Elf3-deficient mice.Elf3-deficient enterocytes express markedly reduced levels of the transforming growth factor beta type II receptor (TGF-beta RII), an inducer of intestinal epithelial differentiation.


CONCLUSIONS
Elf3 is an important regulator of morphogenesis and terminal differentiation of epithelial cell lineages in the small intestine.
Ng
Annie Y-N
AY
Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Victoria, Australia.
Waring
Paul
P
Ristevski
Sika
S
Wang
Caroline
C
Wilson
Trevor
T
Pritchard
Melanie
M
Hertzog
Paul
P
Kola
Ismail
I
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins; D005109:Extracellular Matrix / Q000502:physiology; D007413:Intestinal Mucosa / Q000196:embryology*; D051379:Mice; D009024:Morphogenesis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II