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The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells

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 demonstrat...

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Autores principales: Gao, Yankun, Dutta Banik, Debarghya, Muna, Mutia M, Roberts, Stefan GE, Medler, Kathryn F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555901/
https://www.ncbi.nlm.nih.gov/pubmed/31167803
http://dx.doi.org/10.26508/lsa.201800287
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author Gao, Yankun
Dutta Banik, Debarghya
Muna, Mutia M
Roberts, Stefan GE
Medler, Kathryn F
author_facet Gao, Yankun
Dutta Banik, Debarghya
Muna, Mutia M
Roberts, Stefan GE
Medler, Kathryn F
author_sort Gao, Yankun
collection PubMed
description 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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spelling pubmed-65559012019-06-14 The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells Gao, Yankun Dutta Banik, Debarghya Muna, Mutia M Roberts, Stefan GE Medler, Kathryn F Life Sci Alliance Research Articles 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. Life Science Alliance LLC 2019-06-05 /pmc/articles/PMC6555901/ /pubmed/31167803 http://dx.doi.org/10.26508/lsa.201800287 Text en © 2019 Gao et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Gao, Yankun
Dutta Banik, Debarghya
Muna, Mutia M
Roberts, Stefan GE
Medler, Kathryn F
The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells
title The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells
title_full The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells
title_fullStr The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells
title_full_unstemmed The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells
title_short The WT1–BASP1 complex is required to maintain the differentiated state of taste receptor cells
title_sort wt1–basp1 complex is required to maintain the differentiated state of taste receptor cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555901/
https://www.ncbi.nlm.nih.gov/pubmed/31167803
http://dx.doi.org/10.26508/lsa.201800287
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