Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The molecular mechanisms that drive essential patterning events in the mammalian embryo remain poorly understood. Analysis of transcription factor expression kinetics at peri-gastrulation stages of development suggest Otx2 as a candidate regulator of the definitive endoderm, the precursor of all gut-derived organs. Accordingly, timed OTX2 depletion in gastruloids or during directed differentiation results in abnormal definitive endoderm specification in mouse and human, characterized by altered expression of components and transcriptional targets of the canonical WNT signaling pathway, perturbed adhesion and migration programs, and de-repression of regulators of other lineages. These defects cumulate in impaired foregut formation. Mechanistically, OTX2 is required to activate a subset of endoderm-specific enhancers and to suppress select enhancers of other lineages, allowing timely exit from the primitive streak and correct specification of anterior endoderm. Our results establish OTX2 as an early gut regulator and suggest molecular principles underlying spatiotemporal cell identity conserved across germ layers and species.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.devcel.2025.07.020 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Digital reconstruction of full embryos during early mouse organogenesis.
Cell
August 2025
Department of Cardiac Surgery, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, School of Life Science and
Early organogenesis is a crucial stage in embryonic development, characterized by extensive cell fate specification to initiate organ formation but also by a high susceptibility to developmental defects. Here, we profiled 285 serial sections from six E7.5-E8.
View Article and Find Full Text PDFTBX3 advances the developmental chromatin landscape toward the hepatic fate.
Dev Cell
June 2025
Terry Fox Laboratory, BC Cancer Research Institute, Vancouver, BC V5Z1L3, Canada; Cell and Developmental Biology, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T1Z4, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T1Z4, Canada; School of
By mapping histone modifications in a human stem cell model of hepatic differentiation, we identified an enhancer landscape that is dynamic and stage specific, with many primed at the definitive endoderm stage. While hepatic enhancers gained active histone modifications, non-hepatic enhancers lost H3K4me1 after hepatic specification. T-box transcription factor 3 (TBX3) was found to bind to hepatic enhancers and promoters.
View Article and Find Full Text PDFDuring gastrulation, dynamic interplay among cell signaling pathways dictates cell fate decisions. While extensive studies have elucidated their critical roles in morphological regulation, how these signals orchestrate the epigenome to confer developmental competence remains unclear. In this study, we demonstrate that H3K9me3-marked facultative heterochromatin domains undergo global reorganization during differentiation of human pluripotent stem cells into mesoderm and endoderm, which arise through epithelial-mesenchymal transition (EMT), but not into ectoderm, which retains epithelial state.
View Article and Find Full Text PDFMorphology of the larval midgut of the longhorn beetle Rhytidodera bowringii White, 1853 (Coleoptera: Cerambycidae: Cerambycinae).
Protoplasma
September 2025
Guangxi Key Laboratory of Agro-Environment and Agric-Products Safety, National Demonstration Center for Experimental Plant Science Education, College of Agriculture, Guangxi University, Nanning, Guangxi, 530004, China.
The midgut of insects originates from the endoderm. It is located in the central part of the digestive tract and serves as the primary site for chemical digestion and nutrient absorption. The larvae of Cerambycidae are the most destructive life stage.
View Article and Find Full Text PDFEmbryonic development follows a conserved sequence of events across species, yet the pace of development is highly variable and particularly slow in humans. Species-specific developmental timing is largely recapitulated in stem cell models, suggesting a cell-intrinsic clock. Here we use directed differentiation of human embryonic stem cells into neuroectoderm to perform a whole-genome CRISPR-Cas9 knockout screen and show that the epigenetic factors Menin and SUZ12 modulate the speed of PAX6 expression during neural differentiation.
View Article and Find Full Text PDF