Quantitative perturbation-phenotype maps reveal nonlinear responses underlying robustness of PAR-dependent asymmetric cell division.

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences
PLoS Biology Pub Date : 2024-12-09 eCollection Date: 2024-12-01 DOI:10.1371/journal.pbio.3002437
Nelio T L Rodrigues, Tom Bland, KangBo Ng, Nisha Hirani, Nathan W Goehring
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引用次数: 0

Abstract

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.

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来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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