Modeling organ growth in the Drosophila wing disc

Tyler Gibson

A critical challenge for developmental biologists is to understand how a stereotyped organ emerges from the noisy decisions of individual cells.  To what extent are such decisions genetically programmed, and to what extent are they driven by biophysical forces?  As a model system, we are studying the Drosophila wing disc epithelium.  The system is ideal to address such questions, because, as a 2D planar sheet, all microscopic transformations are directly observable.

In order to address the interplay between biophysical and genetic determinants of cell clone morphology, we are studying how a dividing cell’s spindle orientation correlates with neighbor cell geometry.  Our preliminary results suggest that certain neighbor cell geometries attract a dividing cell’s spindle more strongly than others.  In order to address the extent to which this is a purely biophysical phenomenon, we are examining the same geometric correlates in mutant wing discs having aberrant spindle orientations.  The ultimate goal of this work is to demonstrate a relationship between local biophysical forces and global, genetically-encoded programs, which together constitute a feedback and control system.

As an extension of the above work, we are rigorously analyzing the statistical dynamics of epithelial sheet proliferation in terms of geometric parameters.  Using mathematical models, we hope to elucidate general relationships among cell division, cell geometry, and organ geometry.

in vivo tools for functional analysis of microtubule network architecture

Ashleigh Fritz

Understanding the architecture of cytoskeletal networks underlying different epithelial morphologies is critical to understanding the development of tissues and organs.  To expand the molecular toolkit available to test microtubule (MT) function in vivo, we are analyzing the effect of expressing a MT-severing bacterial toxin on MT architecture in Drosophila epithelial cells. Expression of the bacterial gene disrupts the normal cell morphology, leading to more rounded cells and enhanced cell death.  Presently, we are creating a line of flies to co-express the bacterial toxin with p35 to suppress cell death in the MT-deficient cells.  We will also create novel fusion constructs to subcellularly localize the MT-severing activity.  Finally, in collaboration with Jen Gerton, we are attempting to use the Saccharomyces cerevisiae to screen for functional variants of the bacterial protein.

Analysis of nucleokinetics in the Drosophila wing disc

Emily Jo Meyer