About

Eszter Posfai is an Assistant Professor of Molecular Biology at Princeton University, starting her position in January 2019. Her laboratory focuses on understanding mammalian preimplantation embryo formation through quantitative approaches. She is particularly interested in the molecular basis of cell fate decisions and pattern formation in early embryos, exploring how cellular states are controlled and how they can be reproduced in vitro. Her research involves developing advanced genetic tools, such as CRISPR/Cas9-based methods for site-specific DNA insertion, and utilizing sophisticated imaging techniques to measure the dynamics of molecular events during early development. Her work aims to elucidate the mechanisms underlying embryonic patterning, the role of mechanical forces in cell fate decisions, and the molecular mechanisms of totipotency in vivo and in vitro. Posfai's background includes a Ph.D. in Genetics from the Friedrich Miescher Institute in Basel, Switzerland, and a master's degree in Molecular Biology and Genetics from the University of Szeged, Hungary. Her postdoctoral research at the Sickkids Research Institute in Toronto involved studying early cell fate decisions in the mouse embryo and developing genetic tools for single-cell analysis.

Research topics

• Biology
• Cell biology
• Genetics
• Computational biology
• Computer science

Selected publications

• Cyst-ained connections in the mammalian germline

  Current topics in developmental biology/Current Topics in Developmental Biology · 2026-01-01

  book-chapterSenior author
  PublisherDOI

• A live-cell biosensor of in vivo receptor tyrosine kinase activity reveals feedback regulation of a developmental gradient

  Cell Reports · 2025-06-27 · 2 citations

  articleOpen access

  A lack of tools for detecting receptor activity in vivo has limited our ability to fully explore receptor-level control of developmental patterning. Here, we extend phospho-tyrosine tag (pYtag) biosensors to visualize endogenous receptor tyrosine kinase (RTK) activity in Drosophila. We build biosensors for three RTKs that function across developmental stages and tissues. By characterizing Torso::pYtag during embryonic terminal patterning, we find that Torso activity differs from downstream extracellular signal-regulated kinase (ERK) activity in two surprising ways: Torso activity is narrowly restricted to the poles but produces a broader gradient of ERK and decreases over developmental time, while ERK activity is sustained, an effect mediated by ERK pathway-dependent negative feedback. Our results suggest that a narrow domain of Torso activity, tuned in amplitude by negative feedback, locally activates signaling effectors, which diffuse through the syncytial embryo to form the ERK gradient. Altogether, the results of this work highlight the usefulness of pYtags for investigating receptor-level regulation of developmental patterning.

  PublisherOA PDFDOI

• Generative model for the first cell fate bifurcation in mammalian development

  Development · 2025-08-05 · 2 citations

  articleOpen accessSenior author

  The first cell fate bifurcation in mammalian development directs cells toward either the trophectoderm (TE) or inner cell mass (ICM) compartments in pre-implantation embryos. This decision is regulated by the subcellular localization of a transcriptional co-activator YAP and takes place over several progressively asynchronous cleavage divisions. As a result of this asynchrony and variable arrangement of blastomeres, reconstructing the dynamics of the TE/ICM cell specification from fixed embryos is extremely challenging. To address this, we developed a live-imaging approach and applied it to measure pairwise dynamics of nuclear YAP and its direct target genes, CDX2 and SOX2, which are key transcription factors of the TE and ICM, respectively. Using these datasets, we constructed a generative model of the first cell fate bifurcation, which reveals the time-dependent statistics of the TE and ICM cell allocation. In addition to making testable predictions for the joint dynamics of the full YAP/CDX2/SOX2 motif, the model revealed the stochastic nature of the induction timing of the key cell fate determinants and identified the features of YAP dynamics that are necessary or sufficient for this induction. Notably, temporal heterogeneity was particularly prominent for SOX2 expression among ICM cells. As heterogeneities within the ICM have been linked to the initiation of the second cell fate decision in the embryo, understanding the origins of this variability is of key significance. The presented approach reveals the dynamics of the first cell fate choice and lays the groundwork for dissecting the next cell fate decisions in mouse development.

  PublisherOA PDFDOI

• Live imaging endogenous transcription factor dynamics reveals mechanisms of epiblast and primitive endoderm fate segregation

  Current Biology · 2025-07-31 · 6 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Assessment of hepatitis C virus permissiveness in iteratively genetically humanized mice

  Journal of Virology · 2025-09-03

  articleOpen access

  Hepatitis C virus (HCV) is an enveloped, positive-sense single-stranded RNA virus causing chronic infections in over 50 million people who are at risk of developing severe liver disease. Greater understanding of HCV pathogenesis and vaccine development has been hampered by the lack of a fully immunocompetent small-animal model permissive to infection. Rodents are resistant to HCV infection due to a variety of factors at the levels of entry and replication, many of which have been discovered within the past decade. We hypothesized that genetically altering these factors in mice would provide a host environment conducive to infection. Here, we present the generation and characterization of a series of mouse lines bearing humanized alleles for CD81, occludin, TRIM26, and CypA, the murine orthologs for which do not support HCV uptake and replication. Additionally, we knocked out CD302 and CR1L, which restrict HCV infection in mouse hepatocytes. Intravenously, inoculation of mice harboring some or all of these mutant alleles did not increase viremia. To ascertain that mouse adaptive immune responses do not rapidly clear any putative low-level viremia, we engrafted hepatocytes from these genetically complex lines into immunodeficient liver-injury strains. No cohort of mice presented with sustained HC viremia, although we detected low-level viremia in a subset of transplant-recipient mice. Collectively, although these mouse models did not support robust, sustained viremia, these mouse mutant lines represent the most genetically advanced mouse model of HCV infection and will provide an important platform for future genetic host adaptations and/or complementary viral adaptation approaches.IMPORTANCEHepatitis C virus (HCV) presents a significant threat to global health. Despite its prevalence worldwide, there remain significant knowledge gaps regarding immunopathogenesis, oncogenesis, and determinants for vaccine efficacy. This is due to the scarcity of small-animal models for HCV, a virus that only robustly infects human and chimpanzee hepatocytes. In this work, we genetically engineer mice to either humanize or remove several factors that are known to limit HCV infection in mice. We then expose these mice to HCV and assess whether they develop infection over time. To see whether the immune system impacts infection in these modified mice, we transplant liver cells from those mice into ones that lack immune cells and then assess their ability to develop HCV infection. While we did not succeed in generating a mouse that sustains robust viremia, these complex strains nevertheless represent an important platform for further model development.

  PublisherDOI

• Geometric, cell cycle and maternal-to-zygotic transition-associated YAP dynamics during preimplantation embryo development

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-27

  preprintOpen accessSenior authorCorresponding

  During the first cell fate decision in mammalian embryos the inner cell mass cells, which will give rise to the embryo proper and other extraembryonic tissues, segregate from the trophectoderm cells, the precursors of the placenta. Cell fate segregation proceeds in a gradual manner encompassing two rounds of cell division, as well as cell positional and morphological changes. While it is known that the activity of the Hippo signaling pathway and the subcellular localization of its downstream effector YAP dictate lineage specific gene expression, the response of YAP to these dynamic cellular changes remains incompletely understood. Here we address these questions by quantitative live imaging of endogenously tagged YAP while simultaneously monitoring geometric cellular features and cell cycle progression throughout cell fate segregation. We apply a probabilistic model to our dynamic data, providing a quantitative characterization of the mutual effects of YAP and cellular relative exposed area, which has previously been shown to correlate with subcellular YAP localization in fixed samples. Additionally, we study how nuclear YAP levels are influenced by other factors, such as the decreasing pool of maternally provided YAP that is partitioned to daughter cells through cleavage divisions, cell cycle-associated nuclear volume changes, and a delay after divisions in adjusting YAP levels to new cell positions. Interestingly, we find that establishing low nuclear YAP levels required for the inner cell mass fate is largely achieved by passive cell cycle-associated mechanisms. Moreover, contrary to expectations, we find that mechanical perturbations that result in cell shape changes do not influence YAP localization in the embryo. Together our work identifies how various inputs are integrated over a dynamic developmental time course to shape the levels of a key molecular determinant of the first cell fate choice.

  PublisherOA PDFDOI

• <i>In vivo</i> measurements of receptor tyrosine kinase activity reveal feedback regulation of a developmental gradient

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-07

  preprintOpen access

  Abstract A lack of tools for detecting receptor activity in vivo has limited our ability to fully explore receptor-level control of developmental patterning. Here, we extend a new class of biosensors for receptor tyrosine kinase (RTK) activity, the pYtag system, to visualize endogenous RTK activity in Drosophila . We build biosensors for three Drosophila RTKs that function across developmental stages and tissues. By characterizing Torso::pYtag during terminal patterning in the early embryo, we find that Torso activity differs from downstream ERK activity in two surprising ways: Torso activity is narrowly restricted to the poles but produces a broader gradient of ERK, and Torso activity decreases over developmental time while ERK activity is sustained. This decrease in Torso activity is driven by ERK pathway-dependent negative feedback. Our results suggest an updated model of terminal patterning where a narrow domain of Torso activity, tuned in amplitude by negative feedback, locally activates signaling effectors which diffuse through the syncytial embryo to form the ERK gradient. Altogether, this work highlights the usefulness of pYtags for investigating receptor-level regulation of developmental patterning.

  PublisherOA PDFDOI

• Geometric, cell cycle and maternal-to-zygotic transition-associated YAP dynamics during preimplantation embryo development

  Developmental Biology · 2025-05-09 · 1 citations

  articleSenior authorCorresponding
  PublisherDOI

• Epithelial polarization by the planar cell polarity complex is exclusively non–cell autonomous

  Science · 2025-03-20 · 17 citations

  article

  For cells to polarize collectively along a tissue plane, asymmetrically localized planar cell polarity (PCP) complexes must form intercellular contacts between neighboring cells. Yet, it is unknown whether asymmetric segregation of PCP complexes requires cell-cell contact, or if cell autonomous, antagonistic interactions are sufficient for polarization. To test this, we generated mouse chimeras consisting of dual PCP-reporter cells mixed with unlabeled cells that cannot form PCP bridges. In the absence of intercellular interactions, PCP proteins failed to polarize cell autonomously. Rather, PCP-mediated contacts along single cell-cell interfaces were sufficient to sort PCP components to opposite sides of the junction, independent of junction orientation. Thus, intercellular binding of PCP complexes is the critical step that initiates sorting of opposing PCP complexes to generate asymmetry.

  PublisherDOI

• Generative model for the first cell fate bifurcation in mammalian development

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-25 · 3 citations

  preprintOpen accessSenior authorCorresponding

  The first cell fate bifurcation in mammalian development directs cells toward either the trophectoderm (TE) or inner cell mass (ICM) compartments in preimplantation embryos. This decision is regulated by the subcellular localization of a transcriptional co-activator YAP and takes place over several progressively asynchronous cleavage divisions. As a result of this asynchrony and variable arrangement of blastomeres, reconstructing the dynamics of the TE/ICM cell specification from fixed embryos is extremely challenging. To address this, we developed a live imaging approach and applied it to measure pairwise dynamics of nuclear YAP and its direct target genes, CDX2 and SOX2, key transcription factors of TE and ICM, respectively. Using these datasets, we constructed a generative model of the first cell fate bifurcation, which reveals the time-dependent statistics of the TE and ICM cell allocation. In addition to making testable predictions for the joint dynamics of the full YAP/CDX2/SOX2 motif, the model revealed the stochastic nature of the induction timing of the key cell fate determinants and identified the features of YAP dynamics that are necessary or sufficient for this induction. Notably, temporal heterogeneity was particularly prominent for SOX2 expression among ICM cells. As heterogeneities within the ICM have been linked to the initiation of the second cell fate decision in the embryo, understanding the origins of this variability is of key significance. The presented approach reveals the dynamics of the first cell fate choice and lays the groundwork for dissecting the next cell fate bifurcations in mouse development.

  PublisherOA PDFDOI

Frequent coauthors

• Janet Rossant

  Hospital for Sick Children

  19 shared

• Sophie Petropoulos

  Karolinska Institutet

  8 shared

• Fredrik Lanner

  Karolinska University Hospital

  7 shared

• Bradley Joyce

  Princeton University

  6 shared

• Isidora Rovic

  Lunenfeld-Tanenbaum Research Institute

  6 shared

• Andrea Jurisicova

  Sinai Health System

  6 shared

• Stanislav Y. Shvartsman

  Simons Foundation

  5 shared

• Igor Jurišica

  5 shared

Labs

• Posfai LabPI

Education

• PhD, Genetics, Friedrich Miescher Institute for Biomedical Research

  University of Basel

  2010

• MSc, Molecular Biology and Genetics, Biochemistry

  University of Szeged

  2005

• BSc, Biology, Biology

  University of Szeged

  2003