Abstract
During development, the coordinated and sequential action of signals and regulatory factors controls how cells become different from each other and acquire specific fates. This information can be integrated in gene regulatory networks (GRNs) that model these processes over time and consider temporal and spatial changes of gene expression and how these are regulated.During early development, vertebrate sensory organs arise from the pre-placodal region at the border of the neural plate. Subsequently, FGF signalling plays a crucial role in inducing otic-epibranchial progenitors that ultimately give rise to the otic and epibranchial placodes. Downstream of FGF signalling, many transcription factors are activated. However, their regulatory relationships are not very clear. This project uses a bioinformatics approach to establish a GRN to model how multipotent progenitors transit through sequential regulatory states until they are committed to the ear lineage.
To this end, using systematic perturbation experiments, new ear-specific genes have been identified some of which respond early to FGF. Focussing on these early genes, I have used phylogenetic footprinting combined with histone ChIP-seq to identify novel enhancers. Subsequently, I have investigated transcription factor binding sites within these enhancers to identify a small group of common regulators. In parallel, using mRNA-seq and perturbation data, I have reverse-engineered GRNs that recapitulate known interactions and predict new ones. Using a combination of these approaches, I have ultimately enriched a preliminary literature-based GRN by placing otic genes and their interactions into a hierarchy. Thus, this network is a resource for identifying key otic regulators and their targets and provides guidelines for future experiments.
| Date of Award | 1 Apr 2016 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Andrea Streit (Supervisor) & Reiner Schulz (Supervisor) |