SOX2 redirects the developmental fate of the intestinal epithelium toward a premature gastric phenotype.
Various factors play an essential role in patterning the digestive tract. During development, Sox2 and Cdx2 are exclusively expressed in the anterior and the posterior parts of the primitive gut, respectively. However, it is unclear whether these transcription factors influence each other in determining specification of the naïve gut endoderm. We therefore investigated whether Sox2 redirects the fate of the prospective intestinal part of the primitive gut. Ectopic expression of Sox2 in the posterior region of the primitive gut caused anteriorization of the gut toward a gastric-like phenotype. Sox2 activated the foregut transcriptional program, in spite of sustained co-expression of endogenous Cdx2. However, binding of Cdx2 to its genomic targets and thus its transcriptional activity was strongly reduced. Recent findings indicate that endodermal Cdx2 is required to initiate the intestinal program and to suppress anterior cell fate. Our findings suggest that reduced Cdx2 expression by itself is not sufficient to cause anteriorization, but that Sox2 expression is also required. Moreover, it indicates that the balance between Sox2 and Cdx2 function is essential for proper specification of the primitive gut and that Sox2 may overrule the initial patterning of the primitive gut, emphasizing the plasticity of the primitive gut.
Department of Pediatric Surgery,  Erasmus Medical Center, Dr Molewaterplein 50, 3015GE Rotterdam,  The Netherlands.
Lalini
L
Raghoebir
Elvira R M
ER
Bakker
Jason C
JC
Mills
Sigrid
S
Swagemakers
Marjon Buscop-van
MB
Kempen
Anne Boerema-de
AB
Munck
Siska
S
Driegen
Dies
D
Meijer
Frank
F
Grosveld
Dick
D
Tibboel
Ron
R
Smits
Robbert J
RJ
Rottier
D000818:Animals; D000071616:CDX2 Transcription Factor; D049109:Cell Proliferation; D004707:Endoderm / Q000196:embryology / Q000378:metabolism / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism*; D005775:Gastrula / Q000196:embryology* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000196:embryology* / Q000378:metabolism*; D007422:Intestines / Q000196:embryology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013270:Stomach / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors