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Regulation of Drosophila intestinal stem cell maintenance and differentiation by the transcription factor Escargot
Author(s) -
LozaColl Mariano A,
Southall Tony D,
Sandall Sharsti L,
Brand Andrea H,
Jones D Leanne
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201489050
Subject(s) - biology , stem cell , transcription factor , microbiology and biotechnology , notch signaling pathway , cellular differentiation , drosophila melanogaster , ectopic expression , phenotype , downregulation and upregulation , enteroendocrine cell , genetics , gene , signal transduction , endocrinology , endocrine system , hormone
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 ( ISC s). 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.