Identification of late larval stage developmental checkpoints in Caenorhabditis elegans regulated by insulin/IGF and steroid hormone signaling pathways.
Abstract
Organisms in the wild develop with varying food availability. During periods of nutritional
scarcity, development may slow or arrest until conditions improve. The ability to
modulate developmental programs in response to poor nutritional conditions requires
a means of sensing the changing nutritional environment and limiting tissue growth.
The mechanisms by which organisms accomplish this adaptation are not well understood.
We sought to study this question by examining the effects of nutrient deprivation
on Caenorhabditis elegans development during the late larval stages, L3 and L4, a
period of extensive tissue growth and morphogenesis. By removing animals from food
at different times, we show here that specific checkpoints exist in the early L3 and
early L4 stages that systemically arrest the development of diverse tissues and cellular
processes. These checkpoints occur once in each larval stage after molting and prior
to initiation of the subsequent molting cycle. DAF-2, the insulin/insulin-like growth
factor receptor, regulates passage through the L3 and L4 checkpoints in response to
nutrition. The FOXO transcription factor DAF-16, a major target of insulin-like signaling,
functions cell-nonautonomously in the hypodermis (skin) to arrest developmental upon
nutrient removal. The effects of DAF-16 on progression through the L3 and L4 stages
are mediated by DAF-9, a cytochrome P450 ortholog involved in the production of C.
elegans steroid hormones. Our results identify a novel mode of C. elegans growth in
which development progresses from one checkpoint to the next. At each checkpoint,
nutritional conditions determine whether animals remain arrested or continue development
to the next checkpoint.
Type
Journal articleSubject
AnimalsCaenorhabditis elegans
Caenorhabditis elegans Proteins
Cytochrome P-450 Enzyme System
Female
Food
Forkhead Transcription Factors
Gene Expression Regulation, Developmental
Insulin
Larva
Morphogenesis
Phosphorylation
Receptor, Insulin
Receptors, Cytoplasmic and Nuclear
Somatomedins
Starvation
Transcription Factors
Vulva
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https://hdl.handle.net/10161/10398Published Version (Please cite this version)
10.1371/journal.pgen.1004426Publication Info
Schindler, Adam J; Baugh, L Ryan; & Sherwood, David R (2014). Identification of late larval stage developmental checkpoints in Caenorhabditis elegans
regulated by insulin/IGF and steroid hormone signaling pathways. PLoS Genet, 10(6). pp. e1004426. 10.1371/journal.pgen.1004426. Retrieved from https://hdl.handle.net/10161/10398.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
L. Ryan Baugh
Associate Professor of Biology
The Baugh Lab is interested in phenotypic plasticity and physiological adaptation
to variable environmental conditions. We are using the roundworm C. elegans to understand
how animals adapt to starvation using primarily genetic and genomic approaches. We
are studying how development is governed by nutrient availability, how animals survive
starvation, and the long-term consequences of starvation including adult disease and
transgenerational epigenetic inheritance.
David R. Sherwood
Jerry G. and Patricia Crawford Hubbard Professor
The Sherwood lab is interested in understanding mechanisms that drive dynamic cellular
behaviors underlying normal development and human disease. We study 1) How cells invade
into tissues, 2) How stem cells interact with their niches, and 3) How cells control
and interact with extracellular matrix. Our lab primarily examines C. elegans development,
in which simple cellular complexity, amenability to geneti
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