Speaker
Description
The regulation and maintenance of a tissue’s shape and structure is a major outstanding question in developmental biology and plant biology. In this talk, through iterations between experiments and multiscale model simulations that include a mechanistic description of interkinetic nuclear migration, we will show that the local curvature, height, and nuclear positioning of cells in the Drosophila wing imaginal disc are defined by the concurrent patterning of actomyosin contractility, cell-ECM adhesion, ECM stiffness, and interfacial membrane tension [1]. The biologically calibrated model describing both tissue growth and morphogenesis incorporates the spatial patterning of fundamental subcellular properties. Additionally, the model implements for the first time the dynamics of interkinetic nuclear migration within the simulated pseudostratified epithelium. This includes the basal to apical motion of the nucleus, mitotic rounding, and cell division dynamics. Key characteristics of global tissue architecture, such as the local curvature of the basal wing disc epithelium, cell height, and nuclear positioning, serve as metrics for model calibration. The experiments have shown how these physical features are jointly regulated through spatiotemporal dynamics in the localization of pMyoII, β-Integrin, and ECM stiffness. As the disc grows, there are progressive changes in the patterning of key subcellular features such as actomyosin contractility. The predictions made by the model simulations agree with the observed changes in contractility and cell-ECM adhesion during wing disc morphogenesis. AI techniques are incorporated in the model calibration to develop surrogate models to optimize model parameters. In the second half of the talk, aging of yeast cells will be discussed. Understanding the mechanisms of the cellular aging processes is crucial for attempting to extend organismal lifespan and for studying age-related degenerative diseases. Yeast cells divide through budding, providing a classical biological model for studying cellular aging. With their powerful genetics, relatively short cell cycle, and well-established signaling pathways also found in animals, yeast cells offer valuable insights into the aging process. A three-dimensional multi-scale chemical-mechanical model was developed and used to suggest and test hypothesized impacts of aging on bud morphogenesis [2]. Experimentally calibrated model simulations showed that during the early stage of budding, tubular bud shape in one aging mode could be generated by locally inserting new materials at the bud tip, a process guided by the polarized Cdc42 signal. Furthermore, the aspect ratio of the tubular bud could be stabilized during the late stage as was also observed in experiments [2]. The model simulation results suggest that the localization of new cell surface material insertion, regulated by chemical signal polarization, could be weakened due to cellular aging in yeast and other cell types, leading to the change and stabilization of the bud aspect ratio.
Bibliography
@article{kumar2024balancing,
title={Balancing competing effects of tissue growth and cytoskeletal regulation during Drosophila wing disc development},
author={Kumar, Nilay and Rangel Ambriz, Jennifer and Tsai, Kevin and Mim, Mayesha Sahir and Flores-Flores, Marycruz and Chen, Weitao and Zartman, Jeremiah J and Alber, Mark},
journal={Nature Communications},
volume={15},
number={1},
pages={2477},
year={2024},
publisher={Nature Publishing Group UK London}
}
@article{tsai2024study,
title={Study of impacts of two types of cellular aging on the yeast bud morphogenesis},
author={Tsai, Kevin and Zhou, Zhen and Yang, Jiadong and Xu, Zhiliang and Xu, Shixin and Zandi, Roya and Hao, Nan and Chen, Weitao and Alber, Mark},
journal={PLOS Computational Biology},
volume={20},
number={9},
pages={e1012491},
year={2024},
publisher={Public Library of Science San Francisco, CA USA}
}
