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The WT1-BASP1 Complex is Required to Maintain the Differentiated State of Taste Receptor Cells

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Date 2019 Jun 7
PMID 31167803
Citations 6
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Abstract

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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References
1.
Rebello M, Maliphol A, Medler K . Ryanodine Receptors Selectively Interact with L Type Calcium Channels in Mouse Taste Cells. PLoS One. 2013; 8(6):e68174. PMC: 3694925. DOI: 10.1371/journal.pone.0068174. View

2.
Wagner N, Wagner K, Hammes A, Kirschner K, Vidal V, Schedl A . A splice variant of the Wilms' tumour suppressor Wt1 is required for normal development of the olfactory system. Development. 2005; 132(6):1327-36. DOI: 10.1242/dev.01682. View

3.
Szebenyi S, Laskowski A, Medler K . Sodium/calcium exchangers selectively regulate calcium signaling in mouse taste receptor cells. J Neurophysiol. 2010; 104(1):529-38. PMC: 2904227. DOI: 10.1152/jn.00118.2010. View

4.
Rebello M, Medler K . Ryanodine receptors selectively contribute to the formation of taste-evoked calcium signals in mouse taste cells. Eur J Neurosci. 2010; 32(11):1825-35. PMC: 2994989. DOI: 10.1111/j.1460-9568.2010.07463.x. View

5.
Barlow L . Progress and renewal in gustation: new insights into taste bud development. Development. 2015; 142(21):3620-9. PMC: 4647210. DOI: 10.1242/dev.120394. View