Escargot controls somatic stem cell maintenance through the attenuation of the insulin receptor pathway in Drosophila

Rafael Sênos Demarco; Brian J Stack; Alexander M Tang; Justin Voog; Sharsti L Sandall; Tony D Southall; Andrea H Brand; D Leanne Jones

doi:10.1016/j.celrep.2022.110679

Escargot controls somatic stem cell maintenance through the attenuation of the insulin receptor pathway in Drosophila

Cell Rep. 2022 Apr 19;39(3):110679. doi: 10.1016/j.celrep.2022.110679.

Authors

Rafael Sênos Demarco¹, Brian J Stack¹, Alexander M Tang¹, Justin Voog², Sharsti L Sandall², Tony D Southall³, Andrea H Brand⁴, D Leanne Jones⁵

Affiliations

¹ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
³ Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, London SW7 2AZ, UK.
⁴ The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 1QN, UK.
⁵ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Anatomy, Division of Geriatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, Division of Geriatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: leanne.jones@ucsf.edu.

Abstract

Adult stem cells coordinate intrinsic and extrinsic, local and systemic, cues to maintain the proper balance between self-renewal and differentiation. However, the precise mechanisms stem cells use to integrate these signals remain elusive. Here, we show that Escargot (Esg), a member of the Snail family of transcription factors, regulates the maintenance of somatic cyst stem cells (CySCs) in the Drosophila testis by attenuating the activity of the pro-differentiation insulin receptor (InR) pathway. Esg positively regulates the expression of an antagonist of insulin signaling, ImpL2, while also attenuating the expression of InR. Furthermore, Esg-mediated repression of the InR pathway is required to suppress CySC loss in response to starvation. Given the conservation of Snail-family transcription factors, characterizing the mechanisms by which Esg regulates cell-fate decisions during homeostasis and a decline in nutrient availability is likely to provide insight into the metabolic regulation of stem cell behavior in other tissues and organisms.

Keywords: CP: Developmental biology; CP: Stem cell research; Drosophila; ImpL2; InR; cyst stem cells; escargot; insulin; metabolism; testis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult Stem Cells* / metabolism
Animals
Cell Differentiation
Drosophila / metabolism
Drosophila Proteins* / genetics
Drosophila Proteins* / metabolism
Drosophila melanogaster / metabolism
Insulin-Like Growth Factor Binding Proteins / metabolism
Male
Receptor, Insulin / metabolism
Testis
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

Drosophila Proteins
ImpL2 protein, Drosophila
Insulin-Like Growth Factor Binding Proteins
Transcription Factors
Receptor, Insulin

Abstract

Publication types

MeSH terms

Substances

Grants and funding