Biology subjects

Dale, K. J.

Publications and source records attributed to Dale, K. J..

3 recordsLinked to original sources

bioRxiv2026

Cell size overrides ganglion mother cell fate specification in Drosophila

The size of cells varies enormously in biology and how cell size and function are linked are fundamental questions. Asymmetrically dividing Drosophila neural stem cells, also called neuroblasts, produce a large neuroblast and a smaller ganglion mother cell (GMC) at each division. However, why GMCs need to be smaller than neuroblasts has largely remained unexplained. Here, we developed acute and reversible methods to alter daughter-cell size during a single neuroblast division while preserving cortical polarity and asymmetric inheritance of fate determinants. We identify atypical protein kinase C (aPKC) as a regulator of size asymmetry and show that transient and partial co-inhibition of aPKC and Rho kinase (Drok in Drosophila) generates daughters spanning a size range, including size-wise near-symmetric sibling cells while polarity is preserved. We find that above a certain size threshold daughter cells retain neuroblast-like properties despite inheriting GMC determinants: they divide repeatedly, exhibit neuroblast-like cell-cycle timing, and undergo size-wise asymmetric division. Smaller daughters below this threshold instead follow a GMC-like trajectory. Thus, in Drosophila type I neuroblasts, daughter-cell size can act as a regulator of lineage behaviour, overriding inherited fate cues in sufficiently large daughter cells.

developmental biology↗

bioRxiv2019

The effect of Rosovitine on mPSM explants: a real time analysis

Previously we showed, using fixed tissue techniques, that treatment of chick embryos with a family of pharmacological inhibitors yields increased levels of NICD, an increased NICD half life and longer segments (Wiederman et al., 2015). Here we measure the effect of one of the pharmacological perturbations (Roscovtine) using a real time reporter of the somitogenesis clock. After processing the reporter signal using empirical mode decomposition, we measure the oscillator period in mPSM explants and find, in agreement with the previous study, that the period of the segmentation clock increases upon Roscovitine treatment. However, we also make the novel discovery that the differentiation rate of the mPSM tissue also increases upon Roscovitine treatment. Returning to the previous study, we find that the measured increases in somite size and oscillator period are only consistent with the clock and wavefront model if the wavefront velocity also increased.

developmental biology↗

bioRxiv2019

Reconstruction of the phase dynamics of the somitogenesis clock oscillator

In this study we develop a computational framework for the reconstruction of the phase dynamics of the somitogenesis clock oscillator. Our understanding of the somitogenesis clock, a developmental oscillator found in the vertebrate embryo, has been revolutionised by the development of real time reporters of clock gene expression. However, the signals obtained from the real time reporters are typically noisy, nonstationary and spatiotemporally dynamic and there are open questions with regard to how post-processing can be used to both improve the insight gained from a given experiment and to constrain theoretical models. In this study we present a methodology, which is a variant of empirical mode decomposition, that reconstructs the phase dynamics of the somitogenesis clock. After validating the methodology using synthetic datasets, we define a set of metrics that use the reconstructed phase profiles to infer biologically meaningful quantities. We perform experiments in which the signal from a real time reporter of the somitogenesis clock is recorded and reconstruct the phase dynamics. Application of the defined metrics yields results that are consistent with previous experimental observations. Moreover, we extend previous work by developing a gradient descent method for defining automated kymographs and showing that boundary conditions are non-homogeneous. By studying phase dynamics along phase gradient descent trajectories, we show that, consistent with a previous theoretical model, the oscillation frequency is inversely correlated with the phase gradient but that the coefficient is not constant in time. The proposed methodology provides a tool kit for that can be used in the analysis of future experiments and the quantitative observations can be used to guide the development of future mathematical models.

developmental biology↗