Portion of the surface of a Drosophila embryo stained with antibodies that recognize different actin-binding proteins, imaged using fluorescence microscopy.
My lab studies the role of the actin cytoskeleton in morphogenesis and cell differentiation and in differentiated cell function. We use Drosophila as a model system to manipulate the actin cytoskeleton using genetic, molecular and cell biological techni
ques. State-of-the-art in vivo computer-assisted imaging techinques are extensively used in our studies.
The cytoskeleton plays critical roles in normal embryo organization, localization of informational molecules, cell specialization/differentiation, and tissue morphogenesis; thus, our studies provide insight into cellular mechanisms fundamental to multicel
lular organisms. Since the molecules and processes we study are highly conserved across widely diverged species, the insight we gain is broadly applicable.
Three projects are currently being pursued in the lab:
1) We have generated lethal mutations in one of the two cytoplasmic actin genes in Drosophila (actin5c). Animals that fail to express this isoform die, despite the fact that they still express the other isoform. This indicates actin5c expression provide
s a unique function(s) in particular specialized cells/tissues. We are investigating the nature of this requirement. These mutants are the first cytoplasmic actin mutants in mulicellular animals. They provide us with an opportunity to determine whether
isoform-specific amino acid sequence differences affect actin's interaction with actin-binding proteins important for generating the wide variety of actin structures observed in cells and mediating the function of these structures.
2) We are investigating actin cytoskeletal assembly and function using actin capping protein mutants. Capping protein regulates actin filament assembly and is essential for normal development. Partial loss of function mutants show defects in bristle mor
phogenesis and oogenesis, which is caused by abarrent actin structure formation. We are using these mutants as tools to begin to define interactions important for generating appropriate actin structures at the correct time and places.
3) We are studing coordination of actin and microtubule-based transport in neurons and actin-mediated stabilization of determinants important in early embyonic patterning. Recently, we made the surprising discovery that a class VI unconventional myosin (
actin-based motor) is associated with a microtubule-binding protein protein (D-CLIP-190) which has been implicated in microtubule-based vesicle transport. This association is seen in particular structures, presumably vesicles. in nerve axons and in poste
rior pole plasm, where deteminant import for embryo patterning are located. This complex provides us with a unique tool to manipulate processes that involve coordinated actions of these two cytoskeletal systems.