Fibroblast Growth Factor 4, a secreted heparin-binding protein, is a member of the fibroblast growth factor (FGF) family. FGF4 plays an essential role in the midgut patterning as it inhibits the foregut development and promotes the midgut and hindgut identity. Thus FGF4 induces the intestinal fate, repressing anterior markers such as hematopoietically expressed homeobox 1 (HEX1) and enhancing midgut markers such as PDX1 and CDX2. Also, Wnt signaling is essential to the midgut and hindgut development; high Wnt activity is required to repress foregut development and push towards an intestinal fate. As an example, the a fore mentioned transcription factor BARX1, which is expressed during foregut embryogenesis, induces SFRP1 and SFRP2 which in turn inhibit Wnt signaling, thus repressing midgut fate and favoring the foregut fate. Another crucial transcription factor of intestinal specification is CDX2. CDX2 is expressed early during the anterior-posterior formation of the gut tube and is essential for specifying the intestinal endoderm. Wnt induces the expression of CDX2, thus reinforcing its predominant role in intestinal specification.
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