Biology subjects

Goehring, N.

Publications and source records attributed to Goehring, N..

3 recordsLinked to original sources

bioRxiv2023

Nonlinear readout of spatial cues underlies robustness of asymmetric cell division

A key challenge in the development of an organism is to maintain robust phenotypic outcomes in the face of perturbation. Yet, how such robust outcomes are encoded by developmental networks remains poorly explored. Here we use the C. 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. Specifically, our data point towards an intrinsic 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. At the same time, we find that downstream pathways involved in cell size and fate asymmetry are similarly robust to dosage-dependent changes in the local concentrations of PAR proteins, implying non-trivial complexity in translating PAR signals into pathway outputs. We propose that "quantitative decoupling" of symmetry-breaking, polarity, and asymmetric division modules acts to suppress the accumulation of error as embryos move along this 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.

developmental biology↗

bioRxiv2023

Dissecting the subcellular forces sculpting early C. elegans embryos

Embryo shape is determined by individual cell mechanics, intercellular interaction strength, and geometrical constraints. Models based on surface tensions at cell interfaces can predict 3D static cellular arrangements within aggregates. However, predicting the dynamics of such arrangements is challenging due to difficulties in measuring temporal changes in tensions. Here, we characterise the spatiotemporal changes in cellular tensions shaping the early nematode embryo using AFM, live microscopy, and tension inference. Using excoriated embryos, we validate a hybrid inference pipeline that calibrates relative inferred tensions temporally using cortical myosin enrichment and absolute tensions using AFM measurements. Applied to embryos within their native shell, we infer a spatiotemporal map of absolute tensions, revealing that ABa, ABp, and EMS compaction is driven by increased tension at free surfaces, while P2s initial exclusion is due to high tension at intercellular contacts. We uncover a direct and non-affine contribution of cadherins to cell-cell contact tension, comparable to cadherins indirect contribution via actomyosin regulation. HighlightsO_LIP lineage cells have lower cortical tensions than AB lineage cells C_LIO_LIEnrichment of Myosin-II at the cell cortex is a good predictor of cell-medium tension but is not sufficient to determine tension at cell-cell contacts. C_LIO_LIMyosin-informed tension inference allows determination of the spatiotemporal evolution of all surface tensions within the embryo. C_LIO_LIABa, ABp, and EMS compact due to high tensions at their cell-medium interfaces compared to their cell-cell interfaces, while P2 is initially excluded due to high cell-cell contact tensions. C_LIO_LICadherins contribute directly in a non-linear way by reducing cell-cell contact tension by nearly 50%. C_LI Open AccessFor the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.

biophysics↗

bioRxiv2022

Design principles for selective polarization of PAR proteins by cortical flows

Clustering of membrane-associated molecules is thought to promote interactions with the actomyosin cortex, enabling size-dependent transport by actin flows. Consistent with this model, in the C. elegans zygote, anterior segregation of the polarity protein PAR-3 requires oligomerization. However, through direct assessment of advection of PAR proteins, we not only find no links between PAR-3 advection and oligomer size, but also observe efficient advection of both anterior and posterior PAR proteins. Consequently, differential cortex engagement cannot account for selective size-dependent PAR protein transport. Instead, combining experiment and theory we demonstrate that segregation efficiency of PAR proteins by cortical flow is determined by the stability of membrane association, which is enhanced by clustering and specifies persistence of transport. Indeed, stabilizing membrane association was sufficient to invert polarity of a normally posterior PAR protein. Our data therefore indicate that advection of membrane-associated proteins is more pervasive than anticipated and thus cells must tune membrane association dynamics to achieve differential transport by cortical flows.

cell biology↗