Transcriptional regulation of the ciliopathy gene MKS1/mks-1

Meckel Grubber Syndrome (MKS) is a severe ciliopathy. The first identified causal loci of MKS resided in the gene MKS1. The only known transcription factor of MKS1 is Regulatory Factor X (RFX). C. elegans, an organism with well-characterized ciliated neurons, is ideal for studying ciliary genes. Many ciliary genes including MKS1 are conserved in C. elegans. My study aims to find candidate mutants of transcription factor(s) for mks-1, the C. elegans ortholog of MKS1. In order to track in vivo mks-1 expression in C. elegans, I generated a transgenic strain that expressed Green Fluorescence Protein (GFP) driven by mks-1 promoter. I carried out genetic screens to identify mutations that altered GFP fluorescence intensity and expression profile, as a way to search for potential transcription factor(s) for mks-1 in C. elegans. I successfully found an X-linked recessive mutant, which suppresses mks-1 reporter gene expression in subset of labial neurons. The mutant has normal labial neurons development. This research has set up a solid stage for studying the transcriptional regulation of mks-1 and other ciliary genes.