Presenter: Maisey Schering – Biochemistry, Biology
Faculty Mentor(s): Katie Fisher, Daniel Grimes
Session: (In-Person) Poster Presentation
Breaking of left-right (L-R) symmetry is a fundamental part of animal development. To facilitate this, cell to cell communication via extracellular fluid flow plays a critical role. Failure of this communication results in developmental diseases such as congenital heart disease and abnormal L-R positioning of the organs, termed heterotaxia. Understanding the mechanisms by which fluid flow signals control asymmetry is essential for understanding how to treat these diseases. In embryonic development of zebrafish, the model organism of this project, asymmetric flow in Kupffer’s vesicle (KV) breaks L-R symmetry. The flow signal results in asymmetric repression of an mRNA, dand5, triggering asymmetrical development of the emerging organs. How cells sense and transduce fluid flow, leading to dand5 repression, is not understood. My mentor in the Grimes lab, Katie Fisher, performed a literature review that resulted in 90 novel candidate genes which might regulate L-R asymmetry. These genes are all expressed at the right time and place during development to control fluid flow signaling. We are using a CRISPR/Cas9 screen to identify which of these genes are essential for L-R patterning. Several genes of interest have been identified and homozygous lines with these mutations are currently being generated. I will describe our ongoing screening efforts and early results. By completion of this project, we will know how these novel genes act to ultimately control organ asymmetry.