We use epithelial organs and tissues of Drosophila (the fruit fly) to explore the principles and processes that generate functional organs. Our favorite model organ is the pupal eye. This beautiful, ordered tissue is patterned by a combination of mechanisms that direct cells to acquire specific positions and shapes. These mechanisms include local cell movements and cell competition, cell growth, differentiation and cell signaling. Many cells are removed by apoptosis (programmed cell death).
Our studies focus on a conserved adaptor protein Cindr that is crucial for eye development. If expression of cindr is reduced, the eye is severely mis-patterned. This is because Cindr functions to regulate the cytoskeleton and adhesion of retinal cells. In addition, Cindr is important for the survival of retinal cells.
How does Cindr regulate these important processes? To address this fundamental question, we begin by finding partner proteins that interact with Cindr to pattern the eye. Next, we use powerful genetic and imaging strategies to explore the role of these proteins as the eye is patterned. So far, we have examined interactions between Cindr and
- the ArfGAPs and
- Capping proteins that limit actin polymerization.
- the Nephrins, which generate adhesion complexes in the eye.
- JNK signaling.
We still have much to learn about Cindr and its interacting proteins. We predict that, through studying the processes that require Cindr, we will uncover the principles that govern how complex, functional organs are generated. This information will be applicable to the formation and maintenance of our tissues and organs.
The mammalian orthologs of Cindr are Cd2ap and Cin85. So far, Cd2ap has been most well studied in the context of the kidney: it is essential for the correct structure and function of our kidneys. More recently, mutations in Cd2ap were discovered to leave us susceptible to developing Alzheimer’s Disease. Neurobiologists don’t yet know how Cd2ap protects us from Alzheimer’s, but we predict that the way that Cd2ap functions in our neurons shares similarities with how Cindr functions in fly tissues.
If you have questions about our work, Cindr, or the beautiful Drosophila tissues that we use to elucidate the principles of organ development, please do get in touch with us.