Generative model for the first cell fate bifurcation in mammalian development

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

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

Язык: Английский

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Phenotypic analysis of complex bioengineered 3D models

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

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

Язык: Английский

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A model for boundary-driven tissue morphogenesis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

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

Язык: Английский

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A tug-of-war between germ cell motility and intercellular bridges controls germline cyst formation in mice

Current Biology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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