Schaedel, Oren N. and Gerisch, Birgit and Antebi, Adam and Sternberg, Paul W. (2012) Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood. PLoS Biology, 10 (4). Art. No. e1001306. ISSN 1544-9173. PMCID PMC3323525. doi:10.1371/journal.pbio.1001306. https://resolver.caltech.edu/CaltechAUTHORS:20120529-114112675
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Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20120529-114112675
Abstract
Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals.
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Additional Information: | © 2012 Schaedel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received September 2, 2011; Accepted March 2, 2012; Published April 10, 2012. Academic Editor: Gary Ruvkun, Massachusetts General Hospital Havard Medical School, United States of America. Funding: P.W.S is an investigator with the Howard Hughes Medical Institute; O.N.S. was supported by training grant GM07676 and the Caltech Center for Biological Circuit Design. AA was supported by the NIA/NIH (RO1AG027498), the Ellison Medical Foundation, the Max Planck Society, BMBF, and CECAD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Gladys Medina, Barbara Perry, and John DeModena for technical assistance; WormBase; members of the Sternberg laboratory for helpful discussions; and Dr. Amir Sapir, Dr. Hillel Schwartz, and Dr. Andrea Choe for critically reading the manuscript and Dr. Axel Bethke for helpful discussions. Some nematode strains were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources. qPCR was performed in the Millard and Muriel Jacobs Genetics and Genomics Laboratory at the California Institute of Technology. Author Contributions: The author(s) have made the following declarations about their contributions: Conceived and designed the experiments: OS BG AA. Performed the experiments: OS BG. Analyzed the data: OS BG AA PWS. Contributed reagents/materials/analysis tools: OS BG. Wrote the paper: OS BG AA PWS. | ||||||||||||||||||
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Issue or Number: | 4 | ||||||||||||||||||
PubMed Central ID: | PMC3323525 | ||||||||||||||||||
DOI: | 10.1371/journal.pbio.1001306 | ||||||||||||||||||
Record Number: | CaltechAUTHORS:20120529-114112675 | ||||||||||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20120529-114112675 | ||||||||||||||||||
Official Citation: | Schaedel ON, Gerisch B, Antebi A, Sternberg PW (2012) Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood. PLoS Biol 10(4): e1001306. doi:10.1371/journal.pbio.1001306 | ||||||||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||||
ID Code: | 31678 | ||||||||||||||||||
Collection: | CaltechAUTHORS | ||||||||||||||||||
Deposited By: | Jason Perez | ||||||||||||||||||
Deposited On: | 29 May 2012 21:28 | ||||||||||||||||||
Last Modified: | 09 Nov 2021 19:58 |
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