Organization principles of the early Drosophila embryo

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Di Talia, Stefano

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Hur, Woonyung

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2023-03-28T21:42:15Z

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2023-03-28T21:42:15Z

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2022

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Cell Biology

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Self-organization refers to the emergence of an overall order in time and space that results from collective interactions of its individual components. Cells and tissues in biological systems achieve dynamic organizations through self-organization processes. In this dissertation, I show two different organization principles observed from the developing embryos of the fruit fly Drosophila melanogaster: the Histone Locus Body size control and cortical migration of nuclei. The Histone Locus Body (HLB) is an evolutionarily conserved nuclear body that regulates the transcription and processing of histone mRNAs. We show that Drosophila HLBs form through phase separation. During embryogenesis, the size of HLBs is controlled in a precise and dynamic manner that is dependent on the cell cycle and zygotic histone gene activation. Control of HLB growth is achieved by a mechanism integrating nascent mRNAs at the histone locus, which facilitates phase separation, and the nuclear concentration of the scaffold protein multi-sex combs (Mxc), which is controlled by the activity of cyclin-dependent kinases. Reduced Cdk2 activity results in smaller HLBs and the appearance of nascent, misprocessed histone mRNAs. Thus, our experiments identify a mechanism linking nuclear body growth and size with gene expression. The early syncytial Drosophila melanogaster embryo goes through 13 rapid cleavage divisions. Followed by axial expansion during nuclear cycles 4-6, the nuclei collectively migrate to the cortex through cycles 7-9, known as cortical migration. In this study, using light sheet microscopy and quantitative analysis, we track individual nuclei in 3D over the migrating stage and demonstrate that cortical migration is essentially a nuclear packing problem resulting from uniformly expanding nuclear shell or the energids. The division orientation distribution can accurately predict how many nuclei will make it to the next shell, suggesting that the division orientation controls the nuclear fate and overall energids organization. Changes in the cell cycle affects cortical migration phenotype by changing the shell expansion duration rather than speed, which leads to changes in the internuclear distance. The nuclei self-organize in a shell in which inter-nuclear distance potentially matches aster size. Our experimental data and mathematical modeling suggest an additional important role of aster-aster interactions, which is to orient the centrosomes in a way that minimizes crowding. Overall, our data highlights that cortical migration is a self-organized process driven by geometric packing of dividing nuclei.

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https://hdl.handle.net/10161/26834

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Developmental biology

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Cellular biology

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Biophysics

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Cortical migration

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Drosophila melanogaster

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Histone Locus Body

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Nuclear body

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Organization principles of the early Drosophila embryo

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Dissertation

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