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Model of Nkx6.1 function in endocrine precursor cells.

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posted on 2013-01-31, 02:10 authored by Ashleigh E. Schaffer, Brandon L. Taylor, Jacqueline R. Benthuysen, Jingxuan Liu, Fabrizio Thorel, Weiping Yuan, Yang Jiao, Klaus H. Kaestner, Pedro L. Herrera, Mark A. Magnuson, Catherine Lee May, Maike Sander

(A) Expression of Nkx6.1 results in allocation of precursors from all non-beta endocrine lineages to the beta cell lineage. Deletion of Nkx6.1 in endocrine precursors has the opposite effect. When Nkx6.1 is deleted in beta cells, beta cells convert into delta cells, but not into alpha or pancreatic polypeptide (PP)-producing cells. (B) Our study suggests that in endocrine precursors, Nkx6.1 and Isl1 compete for repression and activation, respectively, of the alpha cell fate determinant Arx. We also demonstrate that the expression of Pdx1 in endocrine precursors depends on Nkx6.1. In conjunction with previous studies, showing repression of Pdx1 and Nkx6.1 by Arx [39] and activation of Nkx6.1 by Pdx1 [34], our data support a model whereby cross-repression between Arx and Nkx6.1 confers alpha versus beta cell precursor identity. In beta cell precursors, Nkx6.1 expression is reinforced by Pdx1, which is repressed by Arx in alpha cell precursors.