title: Regulation of Drosophila intestinal stem cell maintenance and differentiation by the transcription factor Escargot.
abstract: Tissue stem cells divide to self-renew and generate differentiated cells to maintain homeostasis. Although influenced by both intrinsic and extrinsic factors, the genetic mechanisms coordinating the decision between self-renewal and initiation of differentiation remain poorly understood. The escargot (esg) gene encodes a transcription factor that is expressed in stem cells in multiple tissues in Drosophila melanogaster, including intestinal stem cells (ISCs). Here, we demonstrate that Esg plays a pivotal role in intestinal homeostasis, maintaining the stem cell pool while influencing fate decisions through modulation of Notch activity. Loss of esg induced ISC differentiation, a decline in Notch activity in daughter enteroblasts (EB), and an increase in differentiated enteroendocrine (EE) cells. Amun, an inhibitor of Notch in other systems, was identified as a target of Esg in the intestine. Decreased expression of esg resulted in upregulation of Amun, while downregulation of Amun rescued the ectopic EE cell phenotype resulting from loss of esg. Thus, our findings provide a framework for further comparative studies addressing the conserved roles of Snail factors in coordinating self-renewal and differentiation of stem cells across tissues and species.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Loza-Coll
authors.affiliation: The Gurdon Institute University of Cambridge, Cambridge, UK.
authors.forename: Tony D
authors.initials: TD
authors.lastname: Southall
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
authors.forename: Sharsti L
authors.initials: SL
authors.lastname: Sandall
authors.affiliation: The Gurdon Institute University of Cambridge, Cambridge, UK.
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Brand
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA leannejones@ucla.edu.
authors.forename: D Leanne
authors.initials: DL
authors.lastname: Jones
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045647:DNA Glycosylases / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000502:physiology; D017353:Gene Deletion; D015870:Gene Expression; D020869:Gene Expression Profiling; D051880:Receptors, Notch / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology*
chemical_list: C546716:Amun protein, Drosophila; D029721:Drosophila Proteins; D051880:Receptors, Notch; C467520:esg protein, Drosophila; D045647:DNA Glycosylases
keywords: Amun; Drosophila; Escargot; Notch; stem cell