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Morphogen gradients can convey position and time in growing tissues
(2023)bioRxivDuring development, cells need to make fate decisions according to their position and the developmental timepoint. Morphogen gradients provide positional information, but how timing is controlled has remained elusive. Here, we show that in morphogen gradients with constant decay length, cells experience transient, hump-shaped concentration profiles if the morphogen source expands in parallel with the uniformly growing tissue. This transient ...Working Paper -
3D Simulation of Tissue Mechanics with Cell Polarization
(2023)bioRxivThe 3D organisation of cells determines tissue function and integrity, and changes dramatically in development and disease. Cell-based simulations have long been used to define the underlying mechanical principles. However, large computational costs have so far limited simulations to either simplified cell geometries or small tissue patches. Here, we present SimuCell3D, a highly efficient open-source program to simulate large tissues in ...Working Paper -
Patterning precision under non-linear morphogen decay and molecular noise
(2022)bioRxivMorphogen gradients can instruct cells about their position in a patterned tissue. Non-linear morphogen decay has been suggested to increase gradient precision by reducing the sensitivity to variability in the morphogen source. Here, we use cell-based simulations to quantitatively compare the positional error of gradients for linear and non-linear morphogen decay. While we confirm that non-linear decay reduces the positional error close ...Working Paper -
Geometric Effects Position Renal Vesicles During Kidney Development
(2022)bioRxivDuring kidney development, reciprocal signalling between the epithelium and the mesenchyme coordinates nephrogenesis with branching morphogenesis of the collecting ducts. The mechanism that positions the renal vesicles, and thus the nephrons, relative to the branching ureteric buds has remained elusive. By combining computational modelling and experiments, we show that geometric effects concentrate the key regulator, WNT9b, at the junctions ...Working Paper -
Hingepoint emergence in mammalian spinal neurulation
(2021)bioRxivNeurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the posterior neuropore changes over time, first showing a median hingepoint, then both the median hingepoint and dorsolateral hingepoints, followed by dorsolateral hingepoints only. The biomechanical mechanism of hingepoint formation in the mammalian neural tube is poorly understood. ...Working Paper -
Morphological study of embryonic Chd8+/- mouse brains using light-sheet microscopy
(2020)bioRxivObjective: Autism spectrum disorder (ASD) encompasses a group of neurodevelopmental conditions that remain poorly understood due to their genetic complexity. CHD8 is a risk allele strongly associated with ASD, and heterozygous Chd8 loss-of-function mice have been reported to exhibit macrocephaly in early postnatal stages. In this work, we sought to identify measurable brain alterations in early embryonic development. Results: We performed ...Working Paper