Biology subjects

Bonavia, S.

Publications and source records attributed to Bonavia, S..

2 recordsLinked to original sources

bioRxiv2025

Morphogen gradients applied basally to human embryonic stem cells to control and dissect tissue patterning

Morphogen gradients are used repeatedly during development to pattern embryonic tissues. Absolute concentrations, duration or even temporal derivative of morphogen concentration have all been proposed to carry positional information. However, establishing the causal relationship between the gradient spatio-temporal profile and resulting cellular diversity and tissue patterning is difficult to address in live embryos because of lack of tools to control those variables. Here, we developed microfluidics devices able to apply spatio-temporally well-defined morphogen landscapes on the basal side of human embryonic stem cells colonies, thus mimicking how BMP4 is delivered to the pluripotent epiblast during mouse gastrulation. Combining live imaging and theoretical modelling, we show that in this configuration the absolute concentration of BMP4 provides positional information and the cell identities emerging during differentiation can vary according to the shape of the gradient. Our toolbox provides a powerful means to dissect the logic of patterning and to engineer tissues precisely.

developmental biology↗

bioRxiv2024

Morphogenetic constrains in the development of gastruloids: implications for mouse gastrulation

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

developmental biology↗