Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UMLS:C0403608 (
ureter
)
9,655
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The organized array of smooth muscle cells (SMCs) and fibroblasts in the walls of visceral tubular organs arises by patterning and differentiation of mesenchymal progenitors surrounding the epithelial lumen. Here, we show that the
TBX2
and TBX3 transcription factors have novel and required roles in regulating these processes in the murine
ureter
. Co-expression of
TBX2
and TBX3 in the inner mesenchymal region of the developing
ureter
requires canonical WNT signaling. Loss of
TBX2
/TBX3 in this region disrupts activity of two crucial drivers of the SMC program,
Foxf1
and BMP4 signaling, resulting in decreased SMC differentiation and increased extracellular matrix. Transcriptional profiling and chromatin immunoprecipitation experiments revealed that
TBX2
/TBX3 directly repress expression of the WNT antagonists
Dkk2
and
Shisa2
, the BMP antagonist
Bmper
and the chemokine
Cxcl12
These findings suggest that
TBX2
/TBX3 are effectors of canonical WNT signaling in the ureteric mesenchyme that promote SMC differentiation by maintaining BMP4 and WNT signaling in the inner region, while restricting CXCL12 signaling to the outer layer of fibroblast-fated mesenchyme.
...
PMID:TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme. 3047 25