Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of Drosophila

In order to maintain tissue homeostasis, cell fate decisions within stem cell lineages have to respond to the needs of the tissue. This coordination of lineage choices with regenerative demand remains poorly characterized. Here, we identify a signal from enteroendocrine cells (EEs) that controls lin...

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Main Authors: Benoît Biteau, Heinrich Jasper
Format: Article
Language:English
Published: Elsevier 2014-06-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124714003994
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author Benoît Biteau
Heinrich Jasper
author_facet Benoît Biteau
Heinrich Jasper
author_sort Benoît Biteau
collection DOAJ
description In order to maintain tissue homeostasis, cell fate decisions within stem cell lineages have to respond to the needs of the tissue. This coordination of lineage choices with regenerative demand remains poorly characterized. Here, we identify a signal from enteroendocrine cells (EEs) that controls lineage specification in the Drosophila intestine. We find that EEs secrete Slit, a ligand for the Robo2 receptor in intestinal stem cells (ISCs) that limits ISC commitment to the endocrine lineage, establishing negative feedback control of EE regeneration. Furthermore, we show that this lineage decision is made within ISCs and requires induction of the transcription factor Prospero in ISCs. Our work identifies a function for the conserved Slit/Robo pathway in the regulation of adult stem cells, establishing negative feedback control of ISC lineage specification as a critical strategy to preserve tissue homeostasis. Our results further amend the current understanding of cell fate commitment within the Drosophila ISC lineage.
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spelling doaj.art-62f16b074a0441c69053143427db099c2022-12-22T00:16:40ZengElsevierCell Reports2211-12472014-06-01761867187510.1016/j.celrep.2014.05.024Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of DrosophilaBenoît Biteau0Heinrich Jasper1Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USAIn order to maintain tissue homeostasis, cell fate decisions within stem cell lineages have to respond to the needs of the tissue. This coordination of lineage choices with regenerative demand remains poorly characterized. Here, we identify a signal from enteroendocrine cells (EEs) that controls lineage specification in the Drosophila intestine. We find that EEs secrete Slit, a ligand for the Robo2 receptor in intestinal stem cells (ISCs) that limits ISC commitment to the endocrine lineage, establishing negative feedback control of EE regeneration. Furthermore, we show that this lineage decision is made within ISCs and requires induction of the transcription factor Prospero in ISCs. Our work identifies a function for the conserved Slit/Robo pathway in the regulation of adult stem cells, establishing negative feedback control of ISC lineage specification as a critical strategy to preserve tissue homeostasis. Our results further amend the current understanding of cell fate commitment within the Drosophila ISC lineage.http://www.sciencedirect.com/science/article/pii/S2211124714003994
spellingShingle Benoît Biteau
Heinrich Jasper
Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of Drosophila
Cell Reports
title Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of Drosophila
title_full Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of Drosophila
title_fullStr Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of Drosophila
title_full_unstemmed Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of Drosophila
title_short Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of Drosophila
title_sort slit robo signaling regulates cell fate decisions in the intestinal stem cell lineage of drosophila
url http://www.sciencedirect.com/science/article/pii/S2211124714003994
work_keys_str_mv AT benoitbiteau slitrobosignalingregulatescellfatedecisionsintheintestinalstemcelllineageofdrosophila
AT heinrichjasper slitrobosignalingregulatescellfatedecisionsintheintestinalstemcelllineageofdrosophila