Regulation of Gastrulation Through Dynamic Patterning in the Drosophila Embryo

Citation

Trisnadi, Nathanie Alna (2015) Regulation of Gastrulation Through Dynamic Patterning in the Drosophila Embryo. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9CJ8BGK. https://resolver.caltech.edu/CaltechTHESIS:09082014-171122678

Abstract

Gene patterning delineates an embryo into precise domains of differential gene expression. However, throughout gastrulation, these patterns are spatiotemporally dynamic due to the changing environment inherent in development and the contribution of multiple inputs. We investigated how the spatiotemporal dynamics of gene expressions influence two processes in the early Drosophila embryo: the establishment of the dorsal-ventral axis and the subsequent mesoderm migration. We found that genes are able to integrate many forms of regulation over space and time in order to refine their expression boundaries and guide gastrulation. Live imaging of the Dorsal transcription factor morphogen gradient revealed spatiotemporal dynamics that never reached steady state. Computational simulations correlated these changes with shifts in the boundaries of downstream target genes. For early mesoderm development, we conducted a screen to ectopically express proteins in specific domains to identify factors involved in migration. We showed that modulation of fibroblast growth factor (FGF) signaling switches between two proteoglycans to transition cells from migration to differentiation. In addition, multiple contributions regulate the complementary expression of cadherins, which is required to provide the proper balance of cell-cell interactions during mesoderm migration. We conclude that the changing environment of the embryo is an important factor during gastrulation and give examples of its impact in defining gene expression domains, supporting specificity of signaling pathways, and regulating adhesion during collective movements.

Thesis Files