Transcriptional Regulation of Left/Right Asymmetry in the Zebrafish Embryo

University Of Virginia Main Campus, Charlottesville VA

Investigators

Abstract

All vertebrate embryos develop along recognizable axes: antero-posterior (head to tail), dorso-ventral (back to belly) and, even less obvious, a left-right (LR) axis characterized by the left or right position of internal organs. The embryonic structure responsible for generating the LR asymmetry has been identified recently, and its function has been analyzed. However the mechanisms leading to its formation are poorly understood. These studies aims to identify and understand the function of novel essential players involved in that process and to characterize the molecular activities that are involved during the different developmental steps leading to the formation of the structure that produces the LR axis. The establishment of LR asymmetry in the zebrafish embryo depends on the activity of motile cilia, present on an epithelium inside a fluid-filled organ called Kupffer's vesicle (KV) that generates a vectorial leftward fluid flow. Formation and differentiation of the KV have been shown to be regulated by several signaling pathways but very little is known about the transcriptional regulation of genes involved in the formation and differentiation of the KV from its precursors, the dorsal forerunner cells (DFCs). This project will characterize the function of novel key players amongst the small set of transcription factors involved in the regulation of KV organogenesis. It will define the developmental step(s) in KV formation that require a functional TEAD1a-Vgll4l transcription complex and identify its relationship with signaling pathways and transcription factors that have been shown to be involved in the formation and/or function of the KV. This project will also generate a complete description of the transcriptome of DFCs and the KV at the different developmental steps of KV organogenesis. It will provide a detailed description of the temporal dynamics of gene expression as well as of the specific role of the transcription factors involved in the KV organogenesis, bringing us close to a complete description, at the molecular level, of the formation of a simple but essential organ of a vertebrate embryo. This project will offer one post-doctoral fellow and two undergraduate students opportunities to engage in cutting-edge research in Developmental Biology and will expose students at all levels of education to the scientific process. It will include: (a) outreach educational activities to local high school students (seminars, science fairs, biowebconferences, workshops at the lab), (b) research experience for undergraduate students and (c) postdoctoral training in a broad range of technologies as well as communication skills essential for career advancement. The scientific results coming out of this project will be communicated through publications in highly ranked journals, presentations at national and international conferences.