Biology subjects

Anlas, K.

Publications and source records attributed to Anlas, K..

6 recordsLinked to original sources

bioRxiv2025

Axial patterning of gastruloids via diverse cell type compositions

The formation of the germ layers and antero-posterior (AP) axial patterning are interlinked milestones of embryogenesis. Gastruloids, in vitro models from aggregated embryonic stem cells (ESCs), permit the study and deconstruction of these events. Gastruloids are successfully generated from ESCs of variable pluripotent states, but it remains unknown how the initial conditions influence cell type composition and to what degree resulting variations in spatial patterning can converge onto an elongated body axis. To address this, we comparatively study aggregates from varying proportions of primed and naive ESCs. Despite differences in AP symmetry-breaking dynamics and distinct trajectories toward either anterior mesodermal or neuro-ectodermal fates, all conditions produce elongated gastruloids. Furthermore, timed modulation of Activin/Nodal signaling in aggregates equalizes AP polarization modes and mixing of initial ESC pluripotent states generates gastruloids with enhanced tissue type diversity. This work therefore uncovers a previously unappreciated developmental flexibility underlying mammalian AP axial patterning.

developmental biology↗

bioRxiv2024

Cell-cell communication controls the timing of gastruloid symmetry-breaking

How cell fate decisions coordinate with tissue-scale morphogenesis remains a major challenge in developmental biology. Gastruloids, three-dimensional aggregates of pluripotent stem cells that self-organise and break symmetry via polarised Brachyury/T expression, provide an ideal system to address this question. By generating gastruloids with defined initial proportions of T-expressing cells we show that fate decisions occur collectively, with cell-fate proportions influencing the transition rates. Mechanical measurements reveal differences in surface tension between T-positive and T-negative tissues, consistent with radial cell sorting. Finally, incorporating fate dynamics and mechanics into a computational model recapitulates the sequential symmetry-breaking events observed in vitro. Our findings identify a mechanochemical mechanism underlying axis formation, and demonstrate how multicellular systems can robustly self-organise without external signalling cues.

biophysics↗

bioRxiv2023

Metabolic control of germ layer proportions through regulation of Nodal and Wnt signalling

During embryonic development, cells exit pluripotency to give rise to the three germ layers. Metabolic pathways influence cell fate decisions by modulating the epigenetic, transcriptional, and signalling states of cells. However, the interplay between metabolism and the major signalling pathways that drive the emergence of ectoderm, mesoderm, and endoderm remains poorly understood. Here, we demonstrate an instructive role of glycolytic activity in activating signalling pathways involved in mesoderm and endoderm induction. Using an in vitro model system for mouse gastrulation, we observed that inhibiting glycolysis prevents the upregulation of primitive streak markers, resulting in a significant increase in ectodermal cell fates at the expense of mesodermal and endodermal lineages. We demonstrate that this relationship is dose-dependent, enabling metabolic control of germ layer proportions through exogenous glucose levels. Mechanistically, we found that glycolysis inhibition leads to the downregulation of Wnt, Nodal, and Fgf signalling. Notably, this metabolic phenotype was rescued by Nodal or Wnt signalling agonists in the absence of glycolytic activity, suggesting that glycolytic activity acts upstream of both signalling pathways. Our work underscores the dependence of specific signalling pathways on metabolic conditions and provides mechanistic insight into the nutritional regulation of cell fate decision making.

developmental biology↗

bioRxiv2021

Dynamics of anteroposterior axis establishment in a mammalian embryo-like system

1.In the mammalian embryo, specification of the anteroposterior (AP) axis demarcates one of the first steps of body plan formation. While this process requires interactions with extra-embryonic tissues in the native embryo, minimal in vitro systems from embryonic stem cells (ESCs) undergo initial AP polarization in the absence of any localized, external cues. This self-organizing potential of stem cells remains not well understood. Here, we study such an initial symmetry breaking event in gastruloids, an established in vitro model for mammalian body plan formation, using the mesodermal marker gene Brachyury or T (Bra/T) to denote the onset of AP axis specification and concomitant germ layer formation. Through aggregate fusion experiments and manipulation of initial culture conditions as well as key developmental signalling pathways, we probe the dynamics of Bra/T polarization. We further conduct single-cell (sc) RNA sequencing of gastruloids at early stages to identify incipient molecular signatures of germ layer commitment and differences between Bra/T+ and Bra/T- populations during as well as after symmetry breaking. Moreover, we transcriptionally compare early development of gastruloids to the mouse embryo and conclude that gastruloids reproducibly undergo AP axis and germ layer specification in a parallel, but distinct manner: While their primed pluripotent cell populations adopt a more mesenchymal state in lieu of an epithelial epiblast-like transcriptome, the emerging mesendodermal lineages in vitro are nevertheless similar to their in vivo equivalents. Altogether, this study provides a comprehensive analysis of self-organized body plan establishment in a minimal in vitro system of early mammalian patterning and highlights the regulative capacity of mESCs, thereby shedding light on underlying principles of axial polarity formation.

developmental biology↗

bioRxiv2020

linus: Conveniently explore, share and present large-scale biological trajectory data from a web browser.

In biology, we are often confronted with information-rich, large-scale trajectory data, but exploring and communicating patterns in such data is often a cumbersome task. Ideally, the data should be wrapped with an interactive visualisation in one concise package that makes it straightforward to create and test hypotheses collaboratively. To address these challenges, we have developed a tool, linus, which makes the process of exploring and sharing 3D trajectories as easy as browsing a website. We provide a python script that reads trajectory data and enriches them with additional features, such as edge bundling or custom axes and generates an interactive web-based visualisation that can be shared offline and online. The goal of linus is to facilitate the collaborative discovery of patterns in complex trajectory data.

bioinformatics↗

bioRxiv2019

Self-organised symmetry breaking in zebrafish reveals feedback from morphogenesis to pattern formation

A fundamental question in developmental biology is how the early embryo breaks initial symmetry to establish the spatial coordinate system later important for the organisation of the embryonic body plan. In zebrafish, this is thought to depend on the inheritance of maternal mRNAs [1-3], cortical rotation to generate a dorsal pole of beta-catenin activity [4-8] and the release of Nodal signals from the yolk syncytial layer (YSL) [9-12]. Recent work aggregating mouse embryonic stem cells has shown that symmetry breaking can occur in the absence of extra-embryonic tissue [19,20]. To test whether this is also true in zebrafish, we separated embryonic cells from the yolk and allowed them to develop as aggregates. These aggregates break symmetry autonomously to form elongated structures with an anterior-posterior pattern. Extensive cell mixing shows that any pre-existing asymmetry is lost prior to the breaking morphological symmetry, revealing that the maternal pre-pattern is not strictly required for early embryo patterning. Following early signalling events after isolation of embryonic cells reveals that a pole of Nodal activity precedes and is required for elongation. The blocking of PCP-dependent convergence and extension movements disrupts the establishment of opposing poles of BMP and Wnt/TCF activity and the patterning of anterior-posterior neural tissue. These results lead us to suggest that convergence and extension plays a causal role in the establishment of morphogen gradients and pattern formation during zebrafish gastrulation.

developmental biology↗