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Dynamic regulation of the dauer decision

Citation

Schaedel, Oren Noah (2011) Dynamic regulation of the dauer decision. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:04272011-021639361

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 mechanisms that guarantee robust execution of a development choice in such environments remain unknown. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it has an advanced toolkit for cellular and genetic manipulations, and can adopt one of two developmental fates depending on environmental conditions. Nematodes grown in favorable conditions (sufficient food, low population density) develop into adults, whereas nematodes grown in unfavorable conditions (insufficient food, high population density) arrest development as a stress-resistant diapause form called dauer. The steroid hormone dafachronic acid (DA), product of DAF-9/cytochrome P450, 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 hypothesize that information from the environment is integrated and reduced to a single cell nonautonomous environmental integrator, thereby explaining the tight binary nature of the developmental fate decision. We propose a fate coordination mechanism in which production of a small amount of DA is amplified, locking in the adult fate. Using a combination of laser ablations and time lapse image analysis, we demonstrate that upon the decision to become an adult, the XXX neuroendocrine cells act as a source releasing DA. As a result, DAF-12 dependent expression of daf-9 in the epidermis is amplified and propagated from anterior to posterior, dispersing high amounts of DA throughout the body. This dispersion of DA drives adult programs in the gonad, epidermis and vulva. Furthermore, we demonstrate that the XXX cells are not necessary for maintaining the adult fate after the signal amplification has started. This indicates that the epidermal amplification also confers the irreversibility of the decision by uncoupling the execution of the decision from the environmental integrator. We propose that this relay serves as a robust fate-locking mechanism to enforce an organism wide binary decision, despite noisy and complex environmental cues.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Polyphenism, Decision making, environmental condition integration, C. elegans, dauer
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Sternberg, Paul W.
Thesis Committee:
  • Elowitz, Michael B. (chair)
  • Wold, Barbara J.
  • Fraser, Scott E. (co-chair)
  • Guo, Chin-Lin
  • Sternberg, Paul W.
Defense Date:11 May 2011
Author Email:orenis1 (AT) gmail.com
Record Number:CaltechTHESIS:04272011-021639361
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:04272011-021639361
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6356
Collection:CaltechTHESIS
Deposited By: Oren Schaedel
Deposited On:27 May 2011 22:15
Last Modified:16 Apr 2013 23:23

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