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The WT1-like transcription factor Klumpfuss maintains lineage commitment of enterocyte progenitors in the Drosophila intestine

Korzelius, Jerome, Azami, Sina, Ronnen-Oron, Tal, Koch, Philipp, Baldauf, Maik, Meier, Elke, Rodriguez-Fernandez, Imilce A., Groth, Marco, Sousa-Victor, Pedro, Jasper, Heinrich and others. (2019) The WT1-like transcription factor Klumpfuss maintains lineage commitment of enterocyte progenitors in the Drosophila intestine. Nature Communications, 10 (1). ISSN 2041-1723. (doi:10.1038/s41467-019-12003-0) (KAR id:81261)

Abstract

In adult epithelial stem cell lineages, the precise differentiation of daughter cells is critical to maintain tissue homeostasis. Notch signaling controls the choice between absorptive and entero-endocrine cell differentiation in both the mammalian small intestine and the Drosophila midgut, yet how Notch promotes lineage restriction remains unclear. Here, we describe a role for the transcription factor Klumpfuss (Klu) in restricting the fate of enteroblasts (EBs) in the Drosophila intestine. Klu is induced in Notch-positive EBs and its activity restricts cell fate towards the enterocyte (EC) lineage. Transcriptomics and DamID profiling show that Klu suppresses enteroendocrine (EE) fate by repressing the action of the proneural gene Scute, which is essential for EE differentiation. Loss of Klu results in differentiation of EBs into EE cells. Our findings provide mechanistic insight into how lineage commitment in progenitor cell differentiation can be ensured downstream of initial specification cues.

Item Type: Article
DOI/Identification number: 10.1038/s41467-019-12003-0
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Susan Davies
Date Deposited: 15 May 2020 13:55 UTC
Last Modified: 08 Dec 2022 21:14 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/81261 (The current URI for this page, for reference purposes)

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