About

Eric F. Wieschaus is a Professor of Molecular Biology at Princeton University and an Investigator at the Howard Hughes Medical Institute. He is affiliated with the Center for the Physics of Biological Function, an NSF Physics Frontier Center. His research focuses on the molecular mechanisms underlying biological functions, contributing to the understanding of life sciences through his role in the Princeton biophysics and molecular biology communities.

Research topics

• Biology
• Cell biology
• Genetics
• Mathematics
• Physical chemistry
• Chemistry
• Neuroscience
• Geometry
• Statistical physics
• Thermodynamics
• Classical mechanics
• Physics
• Biological system
• Quantum mechanics

Selected publications

• Transcription factor clusters as information transfer agents

  Science Advances · 2025-01-01 · 13 citations

  articleOpen access

  Deciphering how genes interpret information from transcription factor (TF) concentrations within the cell nucleus remains a fundamental question in gene regulation. Recent advancements have revealed the heterogeneous distribution of TF molecules, posing challenges to precisely decoding concentration signals. Using high-resolution single-cell imaging of the fluorescently tagged TF Bicoid in living Drosophila embryos, we show that Bicoid accumulation in submicrometer clusters preserves the spatial information of the maternal Bicoid gradient. These clusters provide precise spatial cues through intensity, size, and frequency. We further discover that Bicoid target genes colocalize with these clusters in an enhancer-binding affinity-dependent manner. Our modeling suggests that clustering offers a faster sensing mechanism for global nuclear concentrations than freely diffusing TF molecules detected by simple enhancers.

  PublisherDOI

• A model for boundary-driven tissue morphogenesis

  arXiv (Cornell University) · 2025-03-05

  preprintOpen access

  Tissue deformations during morphogenesis can be active, driven by internal processes, or passive, resulting from stresses applied at their boundaries. Here, we introduce the Drosophila hindgut primordium as a model for studying boundary-driven tissue morphogenesis. We characterize its deformations and show that its complex shape changes can be a passive consequence of the deformations of the active regions of the embryo that surround it. First, we find an intermediate characteristic triangular shape in the 3D deformations of the hindgut. We construct a minimal model of the hindgut primordium as an elastic ring deformed by active midgut invagination and germ band extension on an ellipsoidal surface, which robustly captures the symmetry-breaking into this triangular shape. We then quantify the 3D kinematics of the tissue by a set of contours and discover that the hindgut deforms in two stages: an initial translation on the curved embryo surface followed by a rapid breaking of shape symmetry. We extend our model to show that the contour kinematics in both stages are consistent with our passive picture. Our results suggest that the role of in-plane deformations during hindgut morphogenesis is to translate the tissue to a region with anisotropic embryonic curvature and show that uniform boundary conditions are sufficient to generate the observed nonuniform shape change. Our work thus provides a possible explanation for the various characteristic shapes of blastopore-equivalents in different organisms and a framework for the mechanical emergence of global morphologies in complex developmental systems.

  PublisherDOI

• A model for boundary-driven tissue morphogenesis

  Proceedings of the National Academy of Sciences · 2025-09-18 · 3 citations

  articleOpen access

  hindgut primordium as a model for studying boundary-driven tissue morphogenesis. We characterize its deformations and show that its complex shape changes can be a passive consequence of the deformations of the active regions of the embryo that surround it. First, we find an intermediate characteristic "triangular keyhole" shape in the 3D deformations of the hindgut. We construct a minimal model of the hindgut primordium as an elastic ring deformed by active midgut invagination and germ band extension on an ellipsoidal surface, which robustly captures the symmetry-breaking into this triangular keyhole shape. We then quantify the 3D kinematics of the tissue by a set of contours and find that the hindgut deforms in two stages: An initial translation on the curved embryo surface followed by a rapid breaking of shape symmetry. We extend our model to show that the contour kinematics in both stages are consistent with our passive picture. Our results suggest that the role of in-plane deformations during hindgut morphogenesis is to translate the tissue to a region with anisotropic embryonic curvature and show that uniform boundary conditions are sufficient to generate the observed nonuniform shape change. Our work thus provides a possible explanation for the various characteristic shapes of blastopore-equivalents in different organisms and a framework for the mechanical emergence of global morphologies in complex developmental systems.

  PublisherOA PDFDOI

• A model for boundary-driven tissue morphogenesis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-11 · 2 citations

  preprintOpen access

  hindgut primordium as a model for studying boundary-driven tissue morphogenesis. We characterize its deformations and show that its complex shape changes can be a passive consequence of the deformations of the active regions of the embryo that surround it. First, we find an intermediate characteristic triangular shape in the 3D deformations of the hindgut. We construct a minimal model of the hindgut primordium as an elastic ring deformed by active midgut invagination and germ band extension on an ellipsoidal surface, which robustly captures the symmetry-breaking into this triangular shape. We then quantify the 3D kinematics of the tissue by a set of contours and discover that the hindgut deforms in two stages: an initial translation on the curved embryo surface followed by a rapid breaking of shape symmetry. We extend our model to show that the contour kinematics in both stages are consistent with our passive picture. Our results suggest that the role of in-plane deformations during hindgut morphogenesis is to translate the tissue to a region with anisotropic embryonic curvature and show that uniform boundary conditions are sufficient to generate the observed nonuniform shape change. Our work thus provides a possible explanation for the various characteristic shapes of blastopore-equivalents in different organisms and a framework for the mechanical emergence of global morphologies in complex developmental systems.

  PublisherOA PDFDOI

• Computing whole embryo strain maps during gastrulation

  Biophysical Journal · 2024-10-09 · 7 citations

  articleOpen access
  PublisherOA PDFDOI

• Sensitive and Accurate Proteome Profiling of Embryogenesis Using Real-Time Search and TMTproC Quantification

  Molecular & Cellular Proteomics · 2024-12-24 · 5 citations

  articleOpen access

  Multiplexed proteomics has become a powerful tool for investigating biological systems. Using balancer-peptide conjugates (e.g., TMTproC complementary ions) in the MS2 spectra for quantification circumvents the ratio distortion problem inherent in multiplexed proteomics. However, TMTproC quantification scans require long Orbitrap transients and extended ion injection times to achieve sufficient ion statistics and spectral resolution. Real-time search (RTS) algorithms have demonstrated increased speed and sensitivity by selectively informing precursor peak quantification. Here, we combine complementary ion quantification with RTS (TMTproC-RTS) to enhance sensitivity while maintaining accuracy and precision in quantitative proteomics at the MS2 level. We demonstrate the utility of this method by quantifying protein dynamics during the embryonic development of Drosophila melanogaster (fly), Ciona robusta (sea squirt), and Xenopus laevis (frog). We quantify 7.8k, 8.6k, and 12.7k proteins in each organism, which is an improvement of 12%, 13%, and 14%, respectively, compared with naive TMTproC analysis. For all three organisms, the newly acquired data outperform previously published datasets and provide a diverse, deep, and accurate database of protein dynamics during embryogenesis, which will advance the study of evolutionary comparison in early embryogenesis.

  PublisherOA PDFDOI

• The Geometric Basis of Epithelial Convergent Extension

  eLife · 2024-07-29 · 2 citations

  preprintOpen access

  Abstract Shape changes of epithelia during animal development, such as convergent extension, are achieved through concerted mechanical activity of individual cells. While much is known about the corresponding large scale tissue flow and its genetic drivers, fundamental questions regarding local control of contractile activity on cellular scale and its embryo-scale coordination remain open. To address these questions, we develop a quantitative, model-based analysis framework to relate cell geometry to local tension in recently obtained timelapse imaging data of gastrulating Drosophila embryos. This analysis provides a systematic decomposition of cell shape changes and T1-rearrangements into internally driven, active, and externally driven, passive, contributions. Our analysis provides evidence that germ band extension is driven by active T1 processes that self-organize through positive feedback acting on tensions. More generally, our findings suggest that epithelial convergent extension results from controlled transformation of internal force balance geometry which combines the effects of bottom-up local self-organization with the top-down, embryo-scale regulation by gene expression.

  PublisherDOI

• The geometric basis of epithelial convergent extension

  eLife · 2024-03-26 · 22 citations

  articleOpen access

  Shape changes of epithelia during animal development, such as convergent extension, are achieved through the concerted mechanical activity of individual cells. While much is known about the corresponding large-scale tissue flow and its genetic drivers, fundamental questions regarding local control of contractile activity on the cellular scale and its embryo-scale coordination remain open. To address these questions, we develop a quantitative, model-based analysis framework to relate cell geometry to local tension in recently obtained time-lapse imaging data of gastrulating Drosophila embryos. This analysis systematically decomposes cell shape changes and T1 rearrangements into internally driven, active, and externally driven, passive, contributions. Our analysis provides evidence that germ band extension is driven by active T1 processes that self-organize through positive feedback acting on tensions. More generally, our findings suggest that epithelial convergent extension results from the controlled transformation of internal force balance geometry which combines the effects of bottom-up local self-organization with the top-down, embryo-scale regulation by gene expression.

  PublisherOA PDFDOI

• Author response: The geometric basis of epithelial convergent extension

  2024-12-19

  peer-reviewOpen access

  Active and passive contributions to cell shape change and rearrangements can be distinguished from observed cell geometry, revealing the self-organization mechanisms underlying internally-driven epithelial convergent extension.

  PublisherDOI

• The Geometric Basis of Epithelial Convergent Extension

  eLife · 2024-03-26 · 1 citations

  preprintOpen access

  Abstract Shape changes of epithelia during animal development, such as convergent extension, are achieved through concerted mechanical activity of individual cells. While much is known about the corresponding large scale tissue flow and its genetic drivers, key open questions regard the cell-scale mechanics, e.g. internal vs external driving forces, and coordination, e.g. bottom-up self-organization vs top-down genetic instruction. To address these questions, we develop a quantitative, model-based analysis framework to relate cell geometry to local tension in recently obtained timelapse imaging data of gastrulating Drosophila embryos. This analysis provides a systematic decomposition of cell shape changes and T1–rearrangements into internally driven, active, and externally driven, passive, contributions. Specifically, we find evidence that germ band extension is driven by active T1 processes that self-organize through positive feedback acting on tensions. More generally, our findings suggest that epithelial convergent extension results from controlled transformation of internal force balance geometry which we quantify with a novel quantification tool for local tension configurations.

  PublisherOA PDFDOI

Recent grants

• Oogenesis and Early Embryogenesis in Drosophila

  NIH · $3.8M · 1981–2016

• NIH Grant R01HD015587

  NIH · $1.4M · 2006

• NIH Grant P01CA041086

  NIH · $19.3M · 2007

• NIH Grant R01HD022780

  NIH · $3.2M · 2003

Frequent coauthors

• Thomas Gregor

  Centre National de la Recherche Scientifique

  74 shared

• William Bialek

  Princeton University

  43 shared

• Stefano Di Talia

  Duke Medical Center

  28 shared

• Shelby A. Blythe

  Northwestern University

  27 shared

• Stanislav Y. Shvartsman

  Simons Foundation

  26 shared

• Matthias Kaschube

  Frankfurt Institute for Advanced Studies

  23 shared

• David W. Tank

  Princeton University

  22 shared

• O. Grimm

  Goethe University Frankfurt

  16 shared