PMID- 22505848
OWN - NLM
STAT- MEDLINE
DCOM- 20120807
LR  - 20211021
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 10
IP  - 4
DP  - 2012
TI  - Hormonal signal amplification mediates environmental conditions during 
      development and controls an irreversible commitment to adulthood.
PG  - e1001306
LID - 10.1371/journal.pbio.1001306 [doi]
LID - e1001306
AB  - 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.
FAU - Schaedel, Oren N
AU  - Schaedel ON
AD  - Howard Hughes Medical Institute and Division of Biology, California Institute of 
      Technology, Pasadena, California, United States of America.
FAU - Gerisch, Birgit
AU  - Gerisch B
FAU - Antebi, Adam
AU  - Antebi A
FAU - Sternberg, Paul W
AU  - Sternberg PW
LA  - eng
GR  - T32 GM007616/GM/NIGMS NIH HHS/United States
GR  - GM07676/GM/NIGMS NIH HHS/United States
GR  - R01AG027498/AG/NIA NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - R01 AG027498/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120410
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Cholestenes)
RN  - 0 (Hormones)
RN  - 0 (Pheromones)
RN  - 0 (dafachronic acid)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.- (DAF-9 protein, C elegans)
SB  - IM
CIN - A Novel 3-Hydroxysteroid Dehydrogenase that Regulates Reproductive Development 
      and Longevity.
CIN - Steroids as Central Regulators of Organismal Development and Lifespan.
MH  - Adaptation, Physiological
MH  - Animals
MH  - Caenorhabditis elegans/cytology/*growth & development/metabolism
MH  - Caenorhabditis elegans Proteins/genetics/metabolism
MH  - Cholestenes/*metabolism
MH  - Cytochrome P-450 Enzyme System/genetics/metabolism
MH  - Environment
MH  - Feedback, Physiological
MH  - Hormones/*metabolism/physiology
MH  - Larva/growth & development/metabolism
MH  - Life Cycle Stages
MH  - Phenotype
MH  - Pheromones/metabolism/physiology
MH  - Reproduction
MH  - Subcutaneous Tissue/metabolism
PMC - PMC3323525
COIS- The authors have declared that no competing interests exist.
EDAT- 2012/04/17 06:00
MHDA- 2012/08/08 06:00
PMCR- 2012/04/10
CRDT- 2012/04/17 06:00
PHST- 2011/09/02 00:00 [received]
PHST- 2012/03/02 00:00 [accepted]
PHST- 2012/04/17 06:00 [entrez]
PHST- 2012/04/17 06:00 [pubmed]
PHST- 2012/08/08 06:00 [medline]
PHST- 2012/04/10 00:00 [pmc-release]
AID - PBIOLOGY-D-11-03541 [pii]
AID - 10.1371/journal.pbio.1001306 [doi]
PST - ppublish
SO  - PLoS Biol. 2012;10(4):e1001306. doi: 10.1371/journal.pbio.1001306. Epub 2012 Apr 
      10.