WT1 is a transcriptional activator that controls the boundary between
multipotency and differentiation. The transcriptional cofactor BASP1 binds to
WT1, forming a transcriptional repressor complex that drives differentiation in
cultured cells; however, this proposed mechanism has not been demonstrated in
vivo. We used the peripheral taste system as a model to determine how BASP1
regulates the function of WT1. During development, WT1 is highly expressed in
the developing taste cells while BASP1 is absent. By the end of development,
BASP1 and WT1 are co-expressed in taste cells, where they both occupy the
promoter of WT1 target genes. Using a conditional BASP1 mouse, we demonstrate
that BASP1 is critical to maintain the differentiated state of adult taste cells
and that loss of BASP1 expression significantly alters the composition and
function of these cells. This includes the de-repression of WT1-dependent target
genes from the Wnt and Shh pathways that are normally only transcriptionally
activated by WT1 in the undifferentiated taste cells. Our results uncover a
central role for the WT1–BASP1 complex in maintaining cell
differentiation in vivo.
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