Biology subjects

Steventon, B. J.

Publications and source records attributed to Steventon, B. J..

3 recordsLinked to original sources

bioRxiv2023

Negative feedback on Retinoic Acid by Brachyury guides gastruloid symmetry-breaking

Establishment of the vertebrate body plan requires a combination of extra-embryonic signalling to establish morphogen gradients, and an underlying self-assembly mechanism that contributes to pattern regulation and robustness. Gastruloids are aggregates of mouse embryonic stem cells that break morphological symmetry and polarise Brachyury (Bra) expression in the absence of extra-embryonic signals. However, the mechanism by which symmetry breaking occurs is not yet known. During gastrulation and body axis elongation, retinoic acid (RA) and Cyp26a1 are polarised along the anteroposterior axis, and this is critical for balancing the decision of cells to self-renew or differentiate. We found that symmetry-breaking in gastruloids is coincident with the separation of Aldh1a2 and Cyp26a1 expression, and that feedback from Bra is critical for maintaining polarised Cyp26a1 gene expression in the gastruloid posterior region. Furthermore, we reveal a short temporal window where RA signalling can negatively influence both Bra and Cyp26a1 expression. These observations lead us to suggest a mechanism of how initial gastruloid patterning, subsequent elongation, and evolving network topologies can create defined boundaries of RA signalling that permits proper axial patterning and gastruloid growth.

developmental biology↗

bioRxiv2021

Anterior expansion and posterior addition to the notochord mechanically coordinate embryo axis elongation

During development the embryo body progressively elongates from head-to-tail along the anterior-posterior (AP) axis. Multiple tissues contribute to this elongation through a combination of convergence and extension and/or volumetric growth. How force generated by the morphogenesis of one tissue impacts the morphogenesis of other axial tissues to achieve an elongated axis is not well understood. The notochord, a rod-shaped tissue possessed by all vertebrates, runs across the entire length of the somitic compartment and is flanked on either side by the developing somites in the segmented region of the axis and presomitic mesoderm in the posterior. Cells in the notochord undergo an expansion that is constrained by a stiff sheath of extracellular matrix, that increases the internal pressure in the notochord allowing it to straighten and elongate. Therefore, it is appropriately positioned to play a role in mechanically elongating the somitic compartment. Here, we use multi-photon mediated cell ablation to remove specific regions of the developing notochord and quantify the impact on axis elongation. We show that anterior notochord cell expansion generates a force that displaces notochord cells posteriorly relative to adjacent axial tissues and contributes to the elongation of segmented tissue during post-tailbud stages of development. Crucially, unexpanded cells derived from progenitors at the posterior end of the notochord provide resistance to anterior notochord cell expansion, allowing for force generation across the AP axis. Therefore, notochord cell expansion beginning in the anterior, and addition of cells to the posterior notochord, act as temporally coordinated morphogenetic events that shape the zebrafish embryo AP axis.

developmental biology↗

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↗