RT Journal Article
SR Electronic
T1 The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800287
DO 10.26508/lsa.201800287
VO 2
IS 3
A1 Yankun Gao
A1 Debarghya Dutta Banik
A1 Mutia M Muna
A1 Stefan GE Roberts
A1 Kathryn F Medler
YR 2019
UL https://www.life-science-alliance.org/content/2/3/e201800287.abstract
AB 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.