The cells of epithelial tissues must be correctly organized for the tissue to function correctly. We use the fruit fly (Drosophila) as a model organism to explore how an epithelium becomes organized, with cells of specific shapes, sizes and functions. Our favorite model tissue is the pupal eye: this ordered tissue is patterned by a combination of local cell movements, cell competition, growth, apoptosis, cell signaling and differentiation.
Our studies have focussed on a conserved adaptor protein Cindr that is crucial for eye morphogenesis. If expression of cindr is reduced, the eye is severely mis-patterned. In part, this is because Cindr regulates the cytoskeleton and adhesion, although Cindr is also important for cell survival.
But how does Cindr regulate adhesion and the cytoskeleton? To address this fundamental question we identified proteins that bind to Cindr and then examined their precise role in tissue morphogenesis. 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.
Mask, which functions in the Hippo signaling pathway as a cofactor of Yorkie, also interacts with Cindr. Our investigations of Mask led us to uncover an important role for Hippo signaling in tissue morphogenesis that is independent of Hippo’s well-known role in regulating cell division and survival. We have identified a set of genes that are modified by Mask/Yki activity and that have known or putative roles in regulating adhesion or the cytoskeleton. How this regulation determines the final structure and arrangement of epithelial cells in the fly eye is a major focus of our lab’s research.
Through studying the cellular processes that are regulated by Cindr and/or Hippo signaling in the developing fly eye, we elucidate conserved processes and principles that govern how complex mammalian organs are generated. This information is important because these same processes are used whenever one of our tissues is repaired after damage, or in order to maintain a tissue’s normal homeostasis.
Not surprisingly, the mammalian orthologs of the fly proteins we work with are known to be important in human tissues. Cd2ap and Cin85 (mammalian orthologs of Cindr), are essential for kidney structure, function and repair; mutations in both have been implicated in a range of cancer types; and Cd2ap also functions to protect us from Alzheimer’s Disease. Aberrant Hippo signaling has similarly been implicated as a driver of cancer. Our goal, to utilize Drosophila tissues to understand precisely how it is that Cindr, Mask and other proteins regulate cell function, will greatly inform our understanding of how these often-fatal human diseases arise.
If you have questions about our work or the beautiful Drosophila tissues that we use to elucidate the principles of epithelial organ development, contact us here.
RECENT LAB NEWS :
- Summer 2019: Welcome to Kayla Jaikaran, who has just joined our team as an undergraduate research assistant.
- May 2019: Congrats to Arielle Ashley on her graduation from Wesleyan. Arielle is heading off to med school ….
- March 2019: Our Jove paper is out … we document our method for extracting high-quality RNA from the fly retina.
- July 2018: It’s official, Ruth received tenure and is now an Associate Professor at Wes!
- May 2018: Welcome to Calvin Coffey, who has just joined our team as an undergraduate research student.
- November 2017: Our paper describing how Cindr inhibits JNK to prevent too many cells from dying in the fly pupal eye has been accepted and is now online.
- October 2017: Our paper describing a screen performed by Kwami and Henry to identify E3 ligases that may contribute to eye patterning has been accepted. Read it here.
- Summer 2017 has been busy. First, Miles DeAngelis successfully passed his qualifier exam so he’s now a fully-fledged graduate student in our lab. Congrats Miles! Second, two new undergraduates joined the lab team: Emily McGhie and Harold Pang. Welcome to the lab! Third, we have been awarded an R15 grant from the NIH’s NIGMS. This grant will fund our research for the next 3 years.
- Abigail Matlack joined our research team in February 2017. Welcome Abigail!
- Arielle Ashley joined our research team in September 2016. Welcome!
- In January 2016, Miles DeAngelis joined the lab as a PhD student. Welcome on board Miles!
- January 2016: our paper describing interactions between Cindr and JNK in the wing epithelium has been accepted by Developmental Biology. All those meticulous hours Hannah spent gathering data with the confocal microscope have paid off, not to mention Sam and Tina’s efforts doing many Western Blots. A great team effort.