Robust axis elongation by Nodal-dependent restriction of BMP signaling DOI Creative Commons
Alexandra Schauer,

Kornelija Pranjic-Ferscha,

Robert Hauschild

et al.

Development, Journal Year: 2024, Volume and Issue: 151(4)

Published: Feb. 15, 2024

ABSTRACT Embryogenesis results from the coordinated activities of different signaling pathways controlling cell fate specification and morphogenesis. In vertebrate gastrulation, both Nodal BMP play key roles in germ layer morphogenesis, yet their interplay to coordinate embryo patterning with morphogenesis is still insufficiently understood. Here, we took a reductionist approach using zebrafish embryonic explants study coordination for We show that triggers explant elongation by inducing mesendodermal progenitors but also suppressing activity at site mesendoderm induction. Consistent this, ectopic blocks alignment oriented intercalations, processes during elongation. Translating these ex vivo observations intact showed that, similar explants, suppresses effect on intercalations dorsal domain, thus allowing robust axis These findings suggest dual function effects portion mesendoderm.

Language: Английский

Three‐dimensional stem cell models of mammalian gastrulation DOI Creative Commons
David A. Turner, Alfonso Martínez Arias

BioEssays, Journal Year: 2024, Volume and Issue: 46(12)

Published: Aug. 28, 2024

Abstract Gastrulation is a key milestone in the development of an organism. It period cell proliferation and coordinated cellular rearrangement, that creates outline body plan. Our current understanding mammalian gastrulation has been improved by embryo culture, but there are still many open questions difficult to address because intrauterine embryos low number specimens. In case humans, additional difficulties associated with technical ethical challenges. Over last few years, pluripotent stem models being developed have potential become useful tools understand gastrulation. Here we review these special emphasis on gastruloids provide survey methods produce them robustly, their uses, relationship embryos, prospects as well limitations.

Language: Английский

Citations

8
Pluripotent cell states and fates in human embryo models DOI
Berna Sözen, Patrick Tam, Martín F. Pera

et al.

Development, Journal Year: 2025, Volume and Issue: 152(7)

Published: April 1, 2025

ABSTRACT Pluripotency, the capacity to generate all cells of body, is a defining property transient population epiblast found in pre-, peri- and post-implantation mammalian embryos. As development progresses, undergo dynamic transitions pluripotency states, concurrent with specification extra-embryonic embryonic lineages. Recently, stem cell-based models pre- human have been developed using that capture key properties at different developmental stages. Here, we review early primate development, comparing states vivo cultured pluripotent representative these states. We consider how status starting influences embryo and, turn, what can learn about epiblast. Finally, discuss limitations questions arising from pioneering studies this emerging field.

Language: Английский

Citations

1
Early autonomous patterning of the anteroposterior axis in gastruloids DOI Creative Commons
Kerim Anlaş, Nicola Gritti, Fumio Nakaki

et al.

Development, Journal Year: 2024, Volume and Issue: 151(22)

Published: Nov. 15, 2024

Minimal in vitro systems composed of embryonic stem cells (ESCs) have been shown to recapitulate the establishment anteroposterior (AP) axis. In contrast native embryo, ESC aggregates - such as gastruloids can break symmetry, which is demarcated by polarization mesodermal marker T, autonomously without any localized external cues. However, associated earliest patterning events, spatial restriction cell fates and concomitant transcriptional changes, remain poorly understood. Here, we dissect dynamics AP axis mouse gastruloids, particularly before Wnt stimulation. Through single-cell RNA sequencing, identify key state transitions molecular signatures T+ T- populations underpinning polarization. We also show that this process robust modifications aggregate size. Finally, transcriptomic comparison with embryo indicates develop similar mesendodermal types, despite initial differences their primed pluripotent populations, adopt a more mesenchymal lieu an epiblast-like transcriptome. Hence, our findings suggest possibility alternate states vivo converge onto fates.

Language: Английский

Citations

6
Morphogenetic constrains in the development of gastruloids: implications for mouse gastrulation DOI Creative Commons
Ulla-Maj Fiúza, Sara Bonavia, Pau Pascual-Mas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Mammalian embryonic size is tightly controlled with checkpoints and compensatory mechanisms correcting defects. Here, we take advantage of gastruloids, a stem cell embryoid system not subject to most controls, study the role in emergent properties mammalian embryogenesis. We report that gastruloids exhibit robust morphology transcriptional profiles within range. However, affects dynamics, and, outside range morphogenesis, precision anterior-posterior (AP) axial elongation. Gastruloid elongation exhibits active cellular contractility, requires planar polarity (PCP), adhesion cell-cell contact remodelling. Smaller initiate earlier, correlated an earlier Brachyury polarisation. expression increases tissue fluidity. Axis formation regulated by balance multifoci coalescence timing initiation programme. Sizes beyond can modify relative composition. Very small aggregates have increased neural fate bias, accompanied loss paraxial mesoderm mediated differences Nodal signalling activity.

Language: Английский

Citations

3
Live imaging of paracrine signaling: Advances in visualization and tracking techniques DOI Creative Commons

Eriko Deguchi,

Michiyuki Matsuda, Kenta Terai

et al.

Cell Structure and Function, Journal Year: 2025, Volume and Issue: 50(1), P. 1 - 14

Published: Jan. 1, 2025

Live imaging techniques have revolutionized our understanding of paracrine signaling, a crucial form cell-to-cell communication in biological processes. This review examines recent advances visualizing and tracking factors through four key stages: secretion from producing cells, diffusion extracellular space, binding to target activation intracellular signaling within cells. Paracrine factor can be directly visualized by fluorescent protein tagging ligand, or indirectly the cleavage transmembrane pro-ligands plasma membrane fusion endosomes comprising factors. Diffusion has been studied using such as fluorescence correlation spectroscopy (FCS), recovery after photobleaching (FRAP), decay photoactivation (FDAP), single-molecule tracking. Binding cells various biosensors, including GPCR-activation-based (GRAB) sensors Förster resonance energy transfer (FRET) probes for receptor tyrosine kinases. Finally, is monitored biosensors second messengers, transcription factors, so on. In addition tools, also highlights emerging optogenetic chemogenetic tools triggering release which essential associating outcomes during bioimaging signaling.Key words: live imaging, optogenetics, chemogenetics.

Language: Английский

Citations

0
Beyond mechanosensing: How cells sense and shape their physical environment during development DOI Creative Commons

Matyas Bubna-Litic,

Roberto Mayor

Current Opinion in Cell Biology, Journal Year: 2025, Volume and Issue: 94, P. 102514 - 102514

Published: April 10, 2025

Language: Английский

Citations

0
Design and optimization of a kinase-controlled allosteric switch DOI Creative Commons
Qi Cao, Jared E. Toettcher

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Abstract Post-translational control enables rapid and precise regulation of cell behavior. Despite these advantages, general strategies to build phosphorylation-based synthetic circuits are limited. Here, we reasoned that engineered allostery, a technique has been applied design light- chemically-gated protein switches, could also be used engineer phosphorylation-controlled switches (phospho-switches). Using an allosterically controllable Gal4 transcription factor as scaffold, show classic kinase FRET biosensor architecture can starting point for phospho-switch design. We optimize all features the develop ERK-controlled with 20-fold phosphorylation-dependent change in transcriptional output. Our switch outperforms c-fos promoter, ERK-responsive biosensor, selectivity sensitivity. further our generalized other input kinases controlled targets. This work provides platform new generation kinase-responsive tools biosensing biology applications.

Language: Английский

Citations

0
Extended culture of 2D gastruloids to model human mesoderm development DOI
Bohan Chen, Hina Khan, Zhiyuan Yu

et al.

Nature Methods, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Language: Английский

Citations

0
A modular organization of mammalian gastrulation and the Spemann-Mangold organizer DOI
Alfonso Martínez Arias, André Dias, Alexandra E. Wehmeyer

et al.

Cells and Development, Journal Year: 2025, Volume and Issue: unknown, P. 204031 - 204031

Published: May 1, 2025

Language: Английский

Citations

0
Dynamical systems of fate and form in development DOI Creative Commons
Alex M. Plum, Mattia Serra

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 172, P. 103620 - 103620

Published: June 3, 2025

Developmental biology has long drawn on dynamical systems to understand the diverging fates and emerging form of developing embryo. Cell differentiation morphogenesis unfold in high-dimensional gene-expression spaces position spaces. Yet, their stable reproducible outcomes suggest low-dimensional geometric structures-e.g., fixed points, manifolds, dynamic attracting repelling structures-that organize cell trajectories both This review surveys history recent advances frameworks for development. We focus techniques extracting organizing structures fate decisions morphogenetic movements from experiments, as well interconnections. unifying, perspective aids rationalizing increasingly complex experimental datasets, facilitating principled dimensionality reduction an integrated understanding development, bridging typically distinct domains.

Language: Английский

Citations

0