title: A Transport Model for Estimating the Time Course of ERK Activation in the C. elegans Germline.
abstract: The Caenorhabditis elegans germline is a well-studied model system for investigating the control of cell fate by signaling pathways. Cell signals at the distal tip of the germline promote cell proliferation; just before the loop, signals couple cell maturation to organism-level nutrient status; at the proximal end of the germline, signals coordinate oocyte maturation and fertilization in the presence of sperm. The latter two events require dual phosphorylation and activation of ERK, the effector molecule of the Ras/MAPK cascade. In C. elegans, ERK is known as MPK-1. At this point, none of today's methods for real-time monitoring of dually phosphorylated MPK-1 are working in the germline. Consequently, quantitative understanding of the MPK-1-dependent processes during germline development is limited. Here, we make a step toward advancing this understanding using a model-based framework that reconstructs the time course of MPK-1 activation from a snapshot of a fixed germline. Our approach builds on a number of recent studies for estimating temporal dynamics from fixed organisms, but takes advantage of the anatomy of the germline to simplify the analysis. Our model predicts that the MPK-1 signal turns on ∼30 h into germ cell progression and peaks ∼7 h later.
authors.affiliation: Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
authors.forename: Henry H
authors.initials: HH
authors.lastname: Mattingly
authors.affiliation: The University of Texas Graduate School of Biomedical Sciences and Department of Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: The University of Texas Graduate School of Biomedical Sciences and Department of Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas. Electronic address: sarur@mdanderson.org.
authors.forename: Swathi
authors.initials: S
authors.lastname: Arur
authors.affiliation: Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey. Electronic address: stas@princeton.edu.
authors.forename: Stanislav Y
authors.initials: SY
authors.lastname: Shvartsman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005854:Germ Cells / Q000378:metabolism*; D007700:Kinetics; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D021381:Protein Transport
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases