Embryology of the Gut: Molecular perspectives
Rostral = front / head
Caudal = end / tail
During the development of the gut tube – bumps are made that then
become organ forming domains.
The endodermal sheet of the developing embryo has its rostral – caudal
axis defined during gastrulation by CDX2:
o CDX2 is a transcription factor: caudal type homeobox gene
o Selectively expressed in caudal regions.
o It’s expression in the endodermal sheet / yolk sac determines the
rostral – caudal axis
o CDX2 null mutations:
show a squamous morphology
suggestive of rostral differentiation, basically if you don’t
have CDX2 you are rostral by default.
o If you delete CDX2 – you truncate the gut.
o CDX2 mutants show gene expression patterns caudally more
consistent with the stratified squamous esophageal epithelium
rather than the anus.
o Barrett’s esophageous:
Patches of intestinal – like epithelium in the esophageaus
Caused by abnormal cdx2 expression in the lesions
Occurs due to redifferentiation – this redifferentiation is
thought to be caused by acid reflux coming to the
esophageous.
o CDX2 expression is controlled by WNT signatlling:
With wnt:
Wnt binds to frizzled and causes frizzeled it to be
associated with Arrow
Arrow pulls Axin out of the destruction complex and
it associates with Dsh
This causes Beta – catenin to be expressed /
transolcated into the nucleus. This transcribes CDX2
Without wnt
Destruction complex still intact due to presence of
Axin
B catenin destroyed and unable to translocate to the
nucleus.
Rostral = front / head
Caudal = end / tail
During the development of the gut tube – bumps are made that then
become organ forming domains.
The endodermal sheet of the developing embryo has its rostral – caudal
axis defined during gastrulation by CDX2:
o CDX2 is a transcription factor: caudal type homeobox gene
o Selectively expressed in caudal regions.
o It’s expression in the endodermal sheet / yolk sac determines the
rostral – caudal axis
o CDX2 null mutations:
show a squamous morphology
suggestive of rostral differentiation, basically if you don’t
have CDX2 you are rostral by default.
o If you delete CDX2 – you truncate the gut.
o CDX2 mutants show gene expression patterns caudally more
consistent with the stratified squamous esophageal epithelium
rather than the anus.
o Barrett’s esophageous:
Patches of intestinal – like epithelium in the esophageaus
Caused by abnormal cdx2 expression in the lesions
Occurs due to redifferentiation – this redifferentiation is
thought to be caused by acid reflux coming to the
esophageous.
o CDX2 expression is controlled by WNT signatlling:
With wnt:
Wnt binds to frizzled and causes frizzeled it to be
associated with Arrow
Arrow pulls Axin out of the destruction complex and
it associates with Dsh
This causes Beta – catenin to be expressed /
transolcated into the nucleus. This transcribes CDX2
Without wnt
Destruction complex still intact due to presence of
Axin
B catenin destroyed and unable to translocate to the
nucleus.
