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Kaity, B.

Publications and source records attributed to Kaity, B..

4 recordsLinked to original sources

Dynamic microtubules drive yolk-cytoplasm segregation in the syncytial Drosophila embryo

Yolk-cytoplasm segregation is among the earliest spatial organization events in the developing embryo of many oviparous animals. The segregation process is intimately linked to early embryonic cleavage and pattern formation, and exhibits a wide range of spatial and temporal diversity. However, the underlying cytoskeletal mechanism remains largely unknown, except for a small number of species. Using quantitative live imaging, we investigated yolk segregation in the Drosophila embryo during the syncytial nuclear cycles 11-14. We find that the yolk vesicles move progressively inward in spatial and temporal coordination with the inward expanding microtubule networks that are nucleated from centrosomes positioned at the cortex, whereas cortical actin meshwork remains spatially restricted. Using the gnu RNAi embryo to decouple nuclear migration and division from cytoskeletal dynamics, we establish causality with targeted pharmacological disruption and find that microtubule dynamics is required for yolk segregation, while depolymerization of actin has no discernible effect. In support of a mechanism of growth-propelled passive displacement, microtubule plus end comets come in apparent contact with yolk vesicles, and injected, inert microbeads are displaced towards the embryo center presumably by the same pushing force. These findings identify microtubule polymerization as a predominant driver of yolk-cytoplasm segregation in Drosophila and suggest that diverse cytoskeletal mechanisms evolved to accomplish this crucial reorganization process

developmental biology↗

Emergent Tissue Shapes from the Regulatory Feedback between Morphogens and Cell Growth

The development and regeneration of multicellular organisms require dynamic coordination between cellular behaviors and mechanochemical signals to achieve precise and stable tissue shapes. Plastic organisms, such as planarians, can regenerate, grow, and degrow as adults while maintaining precise whole-body and organ tissue shapes. However, the mechanisms underlying the pathways that coordinate and integrate these signals into the correct balance between cellular growth, mitosis, and apoptosis to form emergent target tissue shapes remain poorly understood. Here, we present a systematic theoretical study of the biological drivers controlling the feedback mechanisms between tissue growth and morphogen signaling. The approach is based on lattice-free, center-based simulations of cell size dynamics, mitosis, and apoptosis governed by both intercellular diffusible morphogen concentrations and mechanical stress between cells to drive their spatial organization. The results demonstrate how different morphogen properties and tissue mechanics form a feedback loop that is essential for the robust regulation of target tissue shapes. Furthermore, we show that stable tissue shapes can emerge from self-regulated patterning processes, such as Turing systems, controlling cellular growth dynamics. A stable feedback loop can form between the emergent morphogen patterns and the dynamics of cellular growth they regulate, as the tissue dynamics define the domain in which morphogens diffuse and hence pattern. Overall, this study highlights the essential role of the feedback loop between morphogen patterning and cellular growth in the regulation of tissue dynamics for stable shape formation. Moreover, this work establishes a framework for further experiments to understand the regulatory dynamics of whole-body development and regeneration using models with high spatiotemporal resolution. SignificanceTight coordination and interpretation of the multitude of signals at different biological scales- from intracellular signals to mechanical interactions-are essential during the development and regeneration of multicellular organisms. In this work, we investigate the leading role of the feedback between mechanochemical signaling networks and tissue shape through cellular behaviors such as growth, proliferation, and apoptosis. This study demonstrates the interdependence between tissue growth and pattern formation mechanisms in the regulation of stable tissue shapes. Overall, this research provides novel mechanistic insights into the formation of tissue shapes through the regulatory feedback interaction between cell growth and patterning dynamics.

biophysics↗

Cyto-architecture constrains a photoactivation induced tubulin gradient in the syncytial Drosophila embryo

Drosophila embryogenesis begins with nuclear division in a common cytoplasm forming a syncytial cell. Morphogen gradient molecules spread across nucleo-cytoplasmic domains to pattern the body axis of the syncytial embryo. The diffusion of molecules across the syncytial nucleo-cytoplasmic domains is potentially constrained by association with the components of cellular architecture, however the extent of restriction has not been examined so far. Here we use photoactivation (PA) to generate a source of cytoplasmic or cytoskeletal molecules in order to monitor the kinetics of their spread in the syncytial Drosophila embryo. Photoactivated PA-GFP and PA-GFP-Tubulin within a fixed anterior area diffused along the antero-posterior axis. These molecules were enriched in cortical cytoplasm above the yolk-filled center suggesting that the cortical cytoplasm is phase separated from the yolk-filled center. The length scales of diffusion were extracted using exponential fits under steady state assumptions. PA-GFP spread to greater distance as compared to PA-GFP-Tubulin. Both gradients were steeper and more restricted when generated in the center of the embryo probably due to a higher density of nucleo-cytoplasmic domains. The length scale of diffusion for PA-GFP-Tubulin gradient increased in mutant embryos containing short plasma membrane furrows and disrupted tubulin cytoskeleton. The PA-GFP gradient shape was unaffected by cyto-architecture perturbation. Taken together, these data show that PA-GFP-Tubulin gradient is largely restricted by its incorporation in the microtubule network and intact plasma membrane furrows. This photoactivation based analysis of protein spread across allows for interpretation of the dependence of gradient formation on the syncytial cyto-architecture.

developmental biology↗

Reprogramming, oscillations and transdifferentiation in epigenetic landscapes

Waddingtons epigenetic landscape provides a phenomenological understanding of the cell differentiation pathways from the pluripotent to mature lineage-committed cell lines. In light of recent successes in the reverse programming process there has been significant interest in quantifying the underlying landscape picture through the mathematics of gene regulatory networks. We investigate the role of time delays arising from multistep chemical reactions and epigenetic rearrangement on the cell differentiation landscape for a realistic two-gene regulatory network, consisting of selfpromoting and mutually inhibiting genes. Our work provides the first theoretical basis of the transdifferentiation process in the presence of delays, where one differentiated cell type can transition to another directly without passing through the undifferentiated state. Additionally, the interplay of time-delayed feedback and a time dependent chemical drive leads to long-lived oscillatory states in appropriate parameter regimes. This work emphasizes the important role played by time-delayed feedback loops in gene regulatory circuits and provides a framework for the characterization of epigenetic landscapes.

systems biology↗