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A key challenge in the development of an organism is to maintain robust phenotypic outcomes in the face of perturbation. Yet, it is often unclear how such robust outcomes are encoded by developmental networks. Here, we use the Caenorhabditis elegans zygote as a model to understand sources of developmental robustness during PAR polarity-dependent asymmetric cell division. By quantitatively linking alterations in protein dosage to phenotype in individual embryos, we show that spatial information in the zygote is read out in a highly nonlinear fashion and, as a result, phenotypes are highly canalized against substantial variation in input signals. Our data point towards robustness of the conserved PAR polarity network that renders polarity axis specification resistant to variations in both the strength of upstream symmetry-breaking cues and PAR protein dosage. Analogously, downstream pathways involved in cell size and fate asymmetry are robust to dosage-dependent changes in the local concentrations of PAR proteins, implying nontrivial complexity in translating PAR concentration profiles into pathway outputs. We propose that these nonlinear signal-response dynamics between symmetry-breaking, PAR polarity, and asymmetric division modules effectively insulate each individual module from variation arising in others. This decoupling helps maintain the embryo along the correct developmental trajectory, thereby ensuring that asymmetric division is robust to perturbation. Such modular organization of developmental networks is likely to be a general mechanism to achieve robust developmental outcomes.
Pubmed ID: 39652540
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Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsCenter that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.
View all literature mentionsCaenorhabditis elegans with name par-2(ok1723)/sC1 [dpy-1(s2170)] III. from WB.
View all literature mentionsCaenorhabditis elegans with name par-1(it324[par-1::GFP::par-1 exon11a]) V. from WB.
View all literature mentionsCaenorhabditis elegans with name par-6(it310[par-6::GFP]) I. from WB.
View all literature mentionsCaenorhabditis elegans with name pkc-3(it309[GFP::pkc-3]) II. from WB.
View all literature mentionsCaenorhabditis elegans with name Caenorhabditis elegans wild isolate. from WB.
View all literature mentionsCaenorhabditis elegans with name par-2(it315[mCherry::par-2]) III. from WB.
View all literature mentionsCaenorhabditis elegans with name par-2(it328[GFP::par-2]) III. from WB.
View all literature mentionsEscherichia coli with name E. coli. from WB.
View all literature mentionsEscherichia coli with name E. coli [F-, mcrA, mcrB, IN(rrnD-rrnE)1, rnc14::Tn10(DE3 lysogen: lacUV5 promoter -T7 polymerase]. from WB.
View all literature mentionsCaenorhabditis elegans with name par-3(it298[par-3::GFP]) III. from WB.
View all literature mentionsCaenorhabditis elegans with name sC1(s2023) [dpy-1(s2170) umnIs21] III. from WB.
View all literature mentionsCaenorhabditis elegans with name spd-5(or213) I. from WB.
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