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1.
Development ; 151(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38742434

ABSTRACT

During mouse development, presomitic mesoderm cells synchronize Wnt and Notch oscillations, creating sequential phase waves that pattern somites. Traditional somitogenesis models attribute phase waves to a global modulation of the oscillation frequency. However, increasing evidence suggests that they could arise in a self-organizing manner. Here, we introduce the Sevilletor, a novel reaction-diffusion system that serves as a framework to compare different somitogenesis patterning hypotheses. Using this framework, we propose the Clock and Wavefront Self-Organizing model that considers an excitable self-organizing region where phase waves form independent of global frequency gradients. The model recapitulates the change in relative phase of Wnt and Notch observed during mouse somitogenesis and provides a theoretical basis for understanding the excitability of mouse presomitic mesoderm cells in vitro.


Subject(s)
Receptors, Notch , Somites , Animals , Mice , Somites/embryology , Somites/metabolism , Receptors, Notch/metabolism , Receptors, Notch/genetics , Mesoderm/embryology , Mesoderm/metabolism , Models, Biological , Body Patterning/genetics , Wnt Proteins/metabolism , Wnt Proteins/genetics , Embryonic Development/genetics , Embryonic Development/physiology , Biological Clocks/physiology
2.
PLoS Biol ; 21(10): e3002315, 2023 10.
Article in English | MEDLINE | ID: mdl-37792696

ABSTRACT

To meet the physiological demands of the body, organs need to establish a functional tissue architecture and adequate size as the embryo develops to adulthood. In the liver, uni- and bipotent progenitor differentiation into hepatocytes and biliary epithelial cells (BECs), and their relative proportions, comprise the functional architecture. Yet, the contribution of individual liver progenitors at the organ level to both fates, and their specific proportion, is unresolved. Combining mathematical modelling with organ-wide, multispectral FRaeppli-NLS lineage tracing in zebrafish, we demonstrate that a precise BEC-to-hepatocyte ratio is established (i) fast, (ii) solely by heterogeneous lineage decisions from uni- and bipotent progenitors, and (iii) independent of subsequent cell type-specific proliferation. Extending lineage tracing to adulthood determined that embryonic cells undergo spatially heterogeneous three-dimensional growth associated with distinct environments. Strikingly, giant clusters comprising almost half a ventral lobe suggest lobe-specific dominant-like growth behaviours. We show substantial hepatocyte polyploidy in juveniles representing another hallmark of postembryonic liver growth. Our findings uncover heterogeneous progenitor contributions to tissue architecture-defining cell type proportions and postembryonic organ growth as key mechanisms forming the adult liver.


Subject(s)
Liver , Zebrafish , Animals , Cell Lineage , Liver/metabolism , Hepatocytes/metabolism , Epithelial Cells , Cell Differentiation , Cell Proliferation
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