The Molecular Basis of Tissue Elasticity and Force Balance During Drosophila Gastrulation

dc.contributor.advisorCollins, James J.en
dc.contributor.committeeMemberDoubrovinski, Konstantinen
dc.contributor.committeeMemberChen, Elizabethen
dc.contributor.committeeMemberDouglas, Peteren
dc.creatorGoldner, Amanda Nicoleen
dc.creator.orcid0000-0002-8471-1277
dc.date.accessioned2024-01-11T20:20:08Z
dc.date.available2024-01-11T20:20:08Z
dc.date.created2021-12
dc.date.issuedDecember 2021
dc.date.submittedDecember 2021
dc.date.updated2024-01-11T20:20:08Z
dc.description.abstractThe mechanics of folding any material rely on two things: the physical forces forming the fold and the material properties of the substance being folded. When working in biological tissue such as an early Drosophila embryo, there is no existing way to directly measure morphogenetic forces, and the relative contributions of forces in various cellular domains remain unknown. To begin, I studied gastrulation in a genetic background where basal membranes never form and cells remain open to the yolk sack throughout the course of VF formation. Strikingly, the VF is still capable of forming in this background. I extensively characterize this phenotype by a combination of electron microscopy and immunofluorescence. My observations rule out a class of popular models of VF formation that would generically predict no folding in the absence of basal membranes. To address this discrepancy, we propose that viscous shear forces play a major role in allowing the furrow to form. We have developed a new computational model that takes cytoplasmic viscous shear into account. In accordance with our observations, our model predicts that basal membranes are dispensable for VF formation. Tissue material properties such as elasticity are also key to fold shape. In vivo tissue deformation experiments show that embryonic tissue is elastic in the stages leading up to gastrulation. Inhibiting F-actin polymerization severely decreases elasticity. I propose that different characteristics of F-actin networks - e.g. branching, remodeling, and crosslinking - are variably responsible for conferring elasticity. It is unclear whether the presence of active forces along actin filaments contributes to tissue elasticity. To this end, I engineered the auxin-inducible degron system to degrade the foremost source of active forces in F-actin networks: myosin II. My design allows us to specifically degrade Drosophila myosin II in under 1hr in vivo. This will allow us to precisely quantify the contribution of myosin II to not only tissue elasticity, but any other feature or developmental process of interest.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1417098723
dc.identifier.urihttps://hdl.handle.net/2152.5/10235
dc.language.isoenen
dc.subjectMyosinsen
dc.subjectActin Cytoskeletonen
dc.subjectActinsen
dc.subjectDrosophilaen
dc.subjectGastrulationen
dc.titleThe Molecular Basis of Tissue Elasticity and Force Balance During Drosophila Gastrulationen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineCell and Molecular Biologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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