Refining Sea Urchin Developmental Gene Regulatory Network Models by Incorporating Wnt Signaling and Information Processed at the hox11/13b Locus

Citation

Cui, Miao (2016) Refining Sea Urchin Developmental Gene Regulatory Network Models by Incorporating Wnt Signaling and Information Processed at the hox11/13b Locus. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9251G6D. https://resolver.caltech.edu/CaltechTHESIS:05232016-193319268

Abstract

The availability of advanced GRN models for sea urchin development presents a unique opportunity to address the function of signaling interactions in cell fate specification at a system-wide level. Here we take a global approach to investigate the regulatory functions of the Wnt signaling system during pre-gastrular development. We examine the embryonic specification processes in order to determine in which embryonic lineages and at what time specific Wnt signals are required. We show a functional divergence among individual Wnt ligands despite their similar and partially overlapped spatial expression. By studying TF activators, we show that expression of wnt genes is tightly controlled and is correlated with their respective functions. In particular Wnt1 and Wnt16, which regulate endodermal specification, are activated by the endoderm regulator Hox11/13b. Motivated by these results and in an effort to further enhance our understanding of endodermal specification, we conducted a cis-regulatory analysis of the hox11/13b gene across a range of developmental stages up to 60 hours post-fertilization. We identify Ets, Eve, and Tcf as direct regulators of hox11/13b, and we show that their combinatorial control drives the endoderm-specific and dynamic early expression of hox11/13b. Furthermore, we show that its late expression in the hindgut is controlled by an inter-modular AND logic gate, in which two separate regulatory modules are both required but neither alone is sufficient.

Thesis Files