Ion channel contributions to developmental signaling in Drosophila

University Of Colorado At Denver, Aurora CO

Investigators

Abstract

How does a single fertilized egg develop into a complex and perfectly patterned organism? Cells need to divide, migrate to the correct location, take on the correct shape, and make all of the parts that are needed for their specialized role. Cells need to communicate with each-other to tell each-other where to go and what to become. Over the last hundred years, researchers have used fruit flies to identify components of the “language” of cell-cell communication required for development of an animal. These developmental chemical signals are essentially the same between flies, worms, birds, and mammals. Recently, the Bates lab discovered that electrical signals are also important for cells to communicate with each-other during development. These electrical signals are conducted through proteins called ion channels. The Bates lab used fruit flies to identify the types of ion channels that are important for a tissue to develop properly. The experiments will determine how some of these ion channels work with the chemical “language” for precise cell-cell communication. This project will also provide science communication classes for graduate students to give them skills to share their research with the community in various forums. In addition this grant will fund ongoing mentoring of high school, undergraduate, and graduate students in their pursuits of scientific careers. Ion channels have emerged as regulators of development, but the mechanism that connects ion channels to conventional developmental signaling pathways is far from clear. Using past NSF funding, the Bates lab showed that bone morphogenetic protein (BMP) signaling requires the inwardly rectifying K+ channel (Irk2) to correctly specify development of the fruit fly wing. This project focuses on the provocative idea that bioelectric signals induce BMP and other developmental signaling. The objective of Aim 1 is to identify the ion channels that contribute to morphogenesis of the fruit fly wing, determine how they influence calcium transients in the wing disc, and determine how these changes to calcium activity impact canonical developmental signaling pathways. The team has chosen to prioritize Stim, Orai, Bestrophin 2, and SERCA for this analysis, and will follow up on other ion channels as time and resources allow. Aim 2 determines the molecular connection between calcium activity in the wing disc and Dpp/BMP release. In addition, broader educational goals include developing and teaching a science communication class for graduate students. Students will utilize skills gained from the class to reach adults in the community through a “science in the news” TED-talk type seminar series and at science comedy events. The Bates lab will continue to mentor high school, undergraduate, and graduate students to include them in transforming current understanding of developmental signaling. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.