Mechanisms Regulating Mesoderm Formation in a Model Spiralian

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

This research will uncover fundamental processes controlling development using an emerging animal model. More specifically, it aims to identify cell interactions and genes that regulate the development of one of three main tissue layers in embryos, the mesoderm, which forms muscles, connective tissue, and other specialized cell types. Comparisons with other animal models will help explain the diversity of animal life on this planet. Studies will also investigate the genes that control a key migratory behavior exhibited by these mesodermal cells. This behavior is exhibited by many different cell types, including cancer cells when they undergo metastasis. Information gathered from these studies will also be used to reconstruct three-dimensional models of embryos for educational purposes. That information will be made available through public websites so that anyone with access to a 3D printer can generate physical models of various stages of development. This will allow students and teachers access to models to better appreciate complex developmental processes, and will foster interdisciplinary interactions between the fields of biology, information technology and engineering. Finally, as this research will involve undergraduate, graduate and post-doctoral students, it will provide valuable opportunities to train future generations of scientists and teachers. This project examines fundamental molecular and cellular mechanisms that regulate mesoderm formation in a model spiralian, the gastropod Crepidula. In addition to the widely conserved endomesoderm, spiralians have a second novel source of mesoderm (ectomesoderm) that may be tied to the origin of larval body plans in this clade. Unlike endomesoderm, ectomesoderm undergoes epithelial-mesenchymal transition (EMT). Cellular and molecular mechanisms regulating the formation of ectomesoderm are poorly understood. Gene regulatory networks (GRNs) have not been constructed for either endo- or ectomesoderm in any spiralian. This project has two specific aims: I. Determine cellular mechanisms that regulate ectomesoderm formation and II. Determine molecular mechanisms that regulate development of spiralian endo- and ectomesoderm. Experiments in Aim I will determine the role of cell-cell interactions vs. cell autonomous factors in regulating ectomesoderm formation by combining lineage tracing, laser cell ablation and fluorescence time-lapse imaging. In Aim II, a combination of gene expression analyses and molecular loss-of-function assays will decipher endo- and ectomesoderm GRNs. Comparisons of these GRNs will validate hypotheses regarding the evolutionary origins of endo- and ectomesoderm. This research may uncover novel interactions between genes regulating mesoderm formation and those involved in EMT. Comparisons with previous studies in other systems will provide a better understanding of gastrulation and body plan evolution amongst the Metazoa. This research will involve undergraduate, graduate and post-doctoral students to provide valuable opportunities to train future scientists and teachers, and will generate valuable reagents and resources for the scientific community. Finally, imaging data will be disseminated through open-access websites to permit 3D printing of physical models of various stages of development, so anyone with access to a 3D printer can create models to appreciate the process of morphogenesis in these embryos. This aspect of the project will foster interdisciplinary interactions between the fields of biology, information technology and engineering.