Presenter: Craig Samuel — Biology
Faculty Mentor(s): Daniel Grimes, Zoe Irons
Session: (In-Person) Oral Panel—Bio-Zebrafish and DNA
Motile cilia are responsible for critical functions in development, including left-right patterning and cerebrospinal fluid flow. Their motility depends on the assembly of outer dynein arms: ATPases which power ciliary beating. Defects in dynein arm function occur in Primary Ciliary Dyskinesia, a disorder affecting 1:15,000–30,000 human births. Daw1 is a cytoplasmic protein thought to be required for cilia beating by controlling import of dynein arms into cilia. Here, I use zebrafish as a model to understand Daw1 function during development and growth. I characterize daw1b1403 mutants, a new daw1 mutant line harboring a 2-amino acid deletion in a conserved region of the protein generated by CRISPR mutagenesis. Defects associated with motile cilia dysfunction in daw1b1403 mutants, including otolith abnormalities, left-right patterning defects, and abnormal body axis curvature are observed. Surprisingly, daw1b1403 mutants exhibit recovery of body curve defects later in development. Consequently, we hypothesize that Daw1 is not essential for cilia motility per se, but only for timely onset of beating over developmental timescales. Importantly, this Daw1 model of delayed cilia motility and body straightening provides an opportunity to study how early embryos can sense, or correct, shape deformations, which is an exciting and relatively unknown aspect of developmental morphogenesis. Ultimately, understanding these processes may help inform our treatments of congenital disorders.