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

Jerome Korzelius (), Sina Azami, Tal Ronnen-Oron, Philipp Koch, Maik Baldauf, Elke Meier, Imilce A. Rodriguez-Fernandez, Marco Groth, Pedro Sousa-Victor and Heinrich Jasper ()
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Jerome Korzelius: Leibniz Institute on Aging–Fritz Lipmann Institute (FLI)
Sina Azami: Leibniz Institute on Aging–Fritz Lipmann Institute (FLI)
Tal Ronnen-Oron: Buck Institute for Research on Aging
Philipp Koch: Leibniz Institute on Aging–Fritz Lipmann Institute (FLI)
Maik Baldauf: Leibniz Institute on Aging–Fritz Lipmann Institute (FLI)
Elke Meier: Leibniz Institute on Aging–Fritz Lipmann Institute (FLI)
Imilce A. Rodriguez-Fernandez: Immunology Discovery, Genentech, Inc.
Marco Groth: Leibniz Institute on Aging–Fritz Lipmann Institute (FLI)
Pedro Sousa-Victor: Buck Institute for Research on Aging
Heinrich Jasper: Leibniz Institute on Aging–Fritz Lipmann Institute (FLI)

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12003-0

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