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A cytoplasmic role of Wnt/β-catenin transcriptional cofactors Bcl9, Bcl9l, and Pygopus in tooth enamel formation

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Sci. Signal.  07 Feb 2017:
Vol. 10, Issue 465, eaah4598
DOI: 10.1126/scisignal.aah4598

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Cytoplasmic functions for transcriptional cofactors in teeth

Bcl9, Bcl9l, and Pygo2 interact with transcription factors, such as the Wnt-regulated protein β-catenin, to regulate gene expression. Cantù et al. reveal that these proteins also have cytoplasmic functions during tooth development and are particularly important for the formation of enamel. Mice lacking both Pygo1 and Pygo2 or both Bcl9 and Bcl9l developed teeth, a process that requires Wnt/β-catenin transcriptional regulation, but the enamel was structurally disorganized and contained less iron than teeth from control mice. Bcl9, Bcl9l, and Pygo2 were present in the cytoplasm of ameloblasts, the cells that secrete enamel proteins, and colocalized in these cells with amelogenin, the main component of enamel. Bcl9 interacted with amelogenin and proteins involved in exocytosis and vesicular trafficking, suggesting that these proteins function in the trafficking or secretion of enamel proteins. These results demonstrate that Bcl9, Bcl9l, and Pygo2 have cytoplasmic functions distinct from their roles as transcriptional cofactors downstream of Wnt signaling.