ABSTRACT: Cilium, a microtubule-based organelle protruding from the cell surface, has crucial roles in embryonic development and human physiology. Our lab reveals that Prostaglandin E2 plays a significant role in ciliogenesis and organ development. Based on these results, we hypothesize that key components in PGE2 signaling pathway participate in cilia formation and function. We have generated ptgs1, ptgs2a, ptger4a and ptger4b mutants using CRISPR/Cas9 technique in zebrafish. These homozygous mutants can survive into adulthood. We are currently in the process of constructing double mutants to eliminate functional redundancy in ciliogenesis. To understand the conserved ciliary roles of PGE2 signaling in mammalian models, we analyzed cilia-associated phenotypes of ptger4-deficient mouse. Our study shows that mouse embryonic fibroblasts (MEF) display deficiency in ptger4 receptor. Furthermore, ptger4-deficient mouse exhibit ciliogenesis defects and abnormal development of lungs, kidneys and tracheas. Together, these findings indicate the conserved regulation of PGE2 in mammalian ciliogenesis.
Key words: Prostaglandin E2 ciliogenesis ptger4 zebrafish mouse .