Investigating the regulation and functioning of RNT-1 and BRO-1 in C. elegans

Thesis

The stem cell-like seam cells of the nematode, Caenorhabditis elegans, represent a tractable and powerful model for studying stem cell biology. rnt-1, the worm homologue of the mammalian RUNX family of transcription factors, together with the CBFβ homologue bro-1, is essential for the proliferation of the seam cells. RUNX genes and CBFβ are important regulators of stem cell development in mammals, and are associated with a variety of cancers. The worm seam cell model offers an opportunity to examine how these genes function in stem cell biology. The aim of this work was to shed light on the genetic network in which bro-1 and rnt-1 function, and to reveal the identity of regulators of these genes as well the downstream targets of the bro-1/rnt-1 pathway.

Here, a number of genes that interact with bro-1 and rnt-1 have been identified. ELT-1, a GATA transcription factor, is shown to be a direct regulator of bro-1. Findings which show that the MEIS gene unc-62 acts upstream of bro-1/rnt-1 and regulates the symmetry of seam cell divisions are also presented. The seam cell marker, scm::gfp, is widely used in studies of the seam cells; here the results of an investigation into its identity and functional links are described. In addition, the mechanism underlying spatial regulation of rnt-1 was examined; this led to the discovery of distinct tissue-specific enhancer modules within an intron of this gene. Finally, interactions between pal-1 and bro-1/rnt-1 are reported and described.

Together, these findings provide a framework for furthering our understanding of the mechanisms and genes associated with the functioning of bro-1 and rnt-1 in the worm.

Authors: Brabin, C

• Publication date: 2012
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: proliferation; C. elegans; enhancers; differentiation; development; stem cells; niche; seam cells
• Subjects: Bioinformatics (life sciences); Biology; Genetics (life sciences); Biochemistry; Development (zoology)