Analysis of insulin-like signaling in C. elegans reveals extensive positive and negative feedback regulation.

The insulin-like signaling system of nematode worms is comparable to that of more complex organisms; it helps regulate a wide range of the animal’s biology, including metabolism, growth, and development. This system is remarkably flexible, with the ability to maintain a physiological steady-state (homeostasis) while also controlling switches between quite different developmental fates (developmental plasticity). A report published in GENETICS reveals the pervasive involvement of both positive and negative feedback in regulating this master pathway in the model nematode Caenorhabditis elegans.

The C. elegans genome encodes one insulin-like receptor and 40 insulin-like signaling proteins. The activity of insulin-like peptides can, in turn, affect the expression of these peptides themselves, yet exactly how this signaling network is regulated remains ambiguous. Kaplan et al. explored the extent of the feedback mechanisms of insulin-like signaling, along with their dependence on nutrient availability.

The worm insulin-like receptor, DAF-2, signals through antagonizing the activity of the transcription factor DAF-16, the nematode ortholog of mammalian FoxO. Because of these opposing functions, daf-2– and daf-16-mutant nematodes were employed to observe how changes in insulin-like signaling affect the expression of insulin-like genes.

Using these mutants under multiple conditions, such as fed vs. starved larval worms, the authors analyzed the expression of insulin-like genes, along with other genes involved in insulin-like signaling, like those in the PI3K pathway.

The authors found extensive feedback regulations within insulin-like signaling; the expression of nearly all detectable insulin-like genes was affected by altering insulin-like signaling, as were some components of the PI3K pathway. These feedback mechanisms were extensive and complex; for example, the well-studied insulin-like protein DAF-28, an agonist of DAF-2, seems to be repressed by DAF-16—thus, DAF-28 is a positive regulator of its own transcription, since activating DAF-2 represses DAF-16.

Overall, considerable evidence for both negative and positive feedback of insulin-like signaling was found; the authors write that this is likely to allow for rapid response to stimuli—like food availability—while still maintaining homeostasis. Further studies will be needed to delve into the precise molecular mechanisms of such feedback systems and to explore similar regulation in other organisms.

CITATION:

Pervasive Positive and Negative Feedback Regulation of Insulin-Like Signaling in Caenorhabditis elegans

Rebecca E. W. Kaplan, Colin S. Maxwell, Nicole Kurhanewicz Codd, L. Ryan Baugh

GENETICS  January 2019 211: 349-361; https://doi.org/10.1534/genetics.118.301702

https://www.genetics.org/content/211/1/349

, , ,

Science Writing and Communications Intern, Genetics Society of America.

View all posts by Marisa Wexler »

Read more in

  • Early Career Leadership Spotlight: Julio Molina Pineda 

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Julio Molina Pineda  Policy and Advocacy University of Arkansas Research Interest  My research interests focus on using model organisms to genetically dissect complex traits related to human disease. My…

  • Peiwei Chen

    Early Career Leadership Spotlight: Peiwei Chen

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Peiwei Chen Accessibility Subcommittee California Institute of Technology Research Interest Far from a harmonious place, the genome is a battleground, where every bit of DNA fights for inheritance and…

  • #Dros23 GSA Poster Award winners

    We are pleased to announce the GSA Poster Award winners from the 64th Annual Drosophila Research Conference! Undergraduate and graduate student members of the GSA were eligible for the awards, and a hard-working team of postdocs volunteered their time as judges. Congratulations to all! Undergraduate Students 1st Place: Sofia Karter Lopez, University of Toronto “Rab11 mediates E-cadherin recycling during…

  • Congratulations to the Fall 2022 DeLill Nasser Awardees!

    GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Fall 2022! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…

  • GENETICS & G3 editors

    New editors join GENETICS, G3 editorial boards

    Several new editors are joining the GSA Journals. We’re excited to welcome Ricardo Zayas to the GENETICS editorial board under the Molecular Genetics of Development section, and on the G3: Genes|Genomes|Genetics board, we welcome Polly Campbell, Kevin Vogel, Joe Parker, and Ricardo Mallarino. Ricardo Zayas Associate Editor Ricardo Zayas is a Professor of Biology at…

  • Worms and Flies Provide Key Clues to Medical Mystery

    This article is part of a series of posts outlining the history and impact of research in experimental organisms. The series is developed in collaboration with the GSA Public Communications and Engagement Committee. By the time Bertrand Might was six months old, it was clear something was amiss. His muscles weren’t developing normally; he was…

  • Congratulations to the 2023 Early Career Leadership Program Cohort!

    The Genetics Society of America (GSA) is excited to announce the latest cohort of student, postdoc, and early-career research leaders joining the Early Career Leadership Program.  Participants receive training and mentoring while serving on committees charged with understanding the needs, interests, concerns, and challenges of early career scientist members of the GSA. As part of…

  • 64th Annual Drosophila Research Conference March 1–5, 2023 Chicago, IL and online

    GSA LOCI: Local Outreach Community Initiatives @ GSA Conferences

    Highlights: Local Outreach Community Initiatives (LOCI): The Genetics Society of America is committed to supporting the communities of the host cities of our conferences. This new year, we are excited to reconnect with our GSA community in meaningful ways within and beyond our existing programming. The GSA membership has created a caring and supportive environment…

  • Headshots of the 5 elected members of the GSA Board of Directors on a black background.

    New members of the GSA Board of Directors: 2023–2025

    We are pleased to announce the election of five new leaders to the GSA Board of Directors: 2023 Vice President/2024 President Mariana Wolfner Distinguished Professor of Molecular Biology and Genetics and Stephen H. Weiss Presidential Fellow My research has focused on the genes and pathways that mediate sexual development and reproduction, primarily in Drosophila. From…

  • Lance David Miller

    Lance David Miller: Lighting Your Own Fire by Finding the Right Resources

    By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…

  • Graça Almeida-Porada: The Importance of Communication in a Technologically Advancing World

    By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…