IDENTIFICATION AND CHARACTERIZATION OF FOXJ1-INDUCED GENES IN MOTILE CILIA

Abstract

Motile cilia beat and direct fluid flow to achieve various outcomes in an animal. Our group previously discovered that the Forkhead domain containing transcription factor Foxj1 is the master regulator of motile cilia differentiation in vertebrates. Given the the fact that there are currently no genome-wide organism based screens for ciliary genes, we first identified the targets of Foxj1 using microarray analysis upon overexpression of Foxj1. By using several validation tools, we showed that the identified list of direct and indirect targets of Foxj1, called as Foxj1-induced genes (FIGs), contain novel motile ciliary genes. Further, I knocked down 50 randomly selected FIGs using morpholinos and found that the knockdown led to the development of cilia-related phenotypes in 31 out of the 50 selected candidates, thereby yielding a hit rate of 62% based on discernable phenotypes in zebrafish embryos.

Additionally, I have reported the characterization of the first leucine rich repeat encoding gene – lrrc9 whose knockdown led to ciliary shortening and ultrastructural abnormalities in the ciliary axonemes.