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2015 ; 399
(2
): 296-305
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Evidence for intermediate mesoderm and kidney progenitor cell specification by
Pax2 and PTIP dependent mechanisms
#MMPMID25617721
Ranghini EJ
; Dressler GR
Dev Biol
2015[Mar]; 399
(2
): 296-305
PMID25617721
show ga
Activation of the Pax2 gene marks the intermediate mesoderm shortly after
gastrulation, as the mesoderm becomes compartmentalized into paraxial,
intermediate, and lateral plate. Using an EGFP knock-in allele of Pax2 to
identify and sort cells of the intermediate mesodermal lineage, we compared gene
expression patterns in EGFP positive cells that were heterozygous or homozygous
null for Pax2. Thus, we identified critical regulators of intermediate mesoderm
and kidney development whose expression depended on Pax2 function. In cell
culture models, Pax2 is thought to recruit epigenetic modifying complex to
imprint activating histone methylation marks through interactions with the
adaptor protein PTIP. In kidney organ culture, conditional PTIP deletion showed
that many Pax2 target genes, which were activated early in renal progenitor
cells, remained on once activated, whereas Pax2 target genes expressed later in
kidney development were unable to be fully activated without PTIP. In Pax2
mutants, we also identified a set of genes whose expression was up-regulated in
EGFP positive cells and whose expression was consistent with a cell fate
transformation to paraxial mesoderm and its derivatives. These data provide
evidence that Pax2 specifies the intermediate mesoderm and renal epithelial cells
through epigenetic mechanisms and in part by repressing paraxial mesodermal fate.