Dissecting mechanisms underlying the Wnt/PCP signaling in endoderm morphogenesis

University Of Iowa, Iowa City IA

Investigators

Abstract

The digestive system is essential for animal function. During the development of the embryo, cells in the deepest tissue layer, which is known as the endoderm, move relative to one another to produce the gut and its associated organs. This movement is required for cell-to-cell communication via a set of proteins that comprise a signaling pathway, whose activity is also essential for many other events during development. The details of how this signaling controls the movement of endodermal cells are not clear, and such knowledge will be crucial to understanding how the gut is formed. The Lin laboratory has identified a subset of the genes in this signaling pathway critical for the above-described movements of the endodermal cells. This research group will apply its expertise in zebrafish genetics and in vivo imaging, as well as established tools, to determine how this signaling pathway controls the movement of endodermal cells during gut development. This study is expected to lead to a clear understanding of how endoderm movements are controlled, which will be broadly applicable to gut development in other animals (including humans). The PI is also passionate about training the next generation of research scientists. She will continue to use zebrafish as a platform for promoting science education at multiple levels, including providing training for postdoctoral fellows and graduate students, research experience for undergraduates, and engaging outreach activities for grade students. The endoderm contributes to the development of the gut and its associated organs. Signaling by the Wnt/planar cell polarity (PCP) pathway has been implicated in endoderm morphogenesis during gut development, but the underlying mechanisms are unclear. The objective of the proposed research is to determine how Wnt/PCP signaling controls endoderm convergence and extension (C&E)—an early step in gut formation, abnormalities in which lead to congenital defects in the digestive system. The Lin laboratory will use transgenic zebrafish lines in which the endoderm is labeled with fluorescent proteins and sensors to perform high-resolution in vivo imaging, in combination with genetic manipulations (global and tissue-specific) and cell biology tools. These will enable them to dissect the mechanisms whereby components of the Wnt/PCP signaling pathway, including its regulator, glypican 4 (Gpc4), orchestrate endodermal C&E. This study is expected to provide a clear understanding of the cellular and molecular mechanisms that control endodermal morphogenesis during gut development. In addition, the results are expected to be applicable to other species and to several other aspects of embryogenesis in which Wnt/PCP signaling is known to play critical roles. 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.