Sall1 in renal stromal progenitors non-cell autonomously restricts the excessive
expansion of nephron progenitors
#MMPMID26511275
Ohmori T
; Tanigawa S
; Kaku Y
; Fujimura S
; Nishinakamura R
Sci Rep
2015[Oct]; 5
(?): 15676
PMID26511275
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The mammalian kidney develops from reciprocal interactions between the
metanephric mesenchyme and ureteric bud, the former of which contains nephron
progenitors. The third lineage, the stroma, fills up the interstitial space and
is derived from distinct progenitors that express the transcription factor Foxd1.
We showed previously that deletion of the nuclear factor Sall1 in nephron
progenitors leads to their depletion in mice. However, Sall1 is expressed not
only in nephron progenitors but also in stromal progenitors. Here we report that
specific Sall1 deletion in stromal progenitors leads to aberrant expansion of
nephron progenitors, which is in sharp contrast with a nephron
progenitor-specific deletion. The mutant mice also exhibited cystic kidneys after
birth and died before adulthood. We found that Decorin, which inhibits
Bmp-mediated nephron differentiation, was upregulated in the mutant stroma. In
contrast, the expression of Fat4, which restricts nephron progenitor expansion,
was reduced mildly. Furthermore, the Sall1 protein binds to many stroma-related
gene loci, including Decorin and Fat4. Thus, the expression of Sall1 in stromal
progenitors restricts the excessive expansion of nephron progenitors in a
non-cell autonomous manner, and Sall1-mediated regulation of Decorin and Fat4
might at least partially underlie the pathogenesis.
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