Date of Award

2022

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

John I. Murray

Second Advisor

Christopher D. Brown

Abstract

Patterning of the anterior-posterior axis is fundamental to animal development. The Wnt pathway plays a major role in this process by activating the expression of posterior genes in animals from worms to humans. This observation raises the question of whether the Wnt pathway or other regulators control the expression of the many anterior-expressed genes. Using time-lapse laser confocal imaging of wild type and RNAi-treated C. elegans embryos, we found that the expression of five anterior-specific genes depends on the Wnt pathway effectors pop-1/TCF and sys-1/β-catenin. We focused further on one of these anterior genes, ref-2/ZIC, a conserved transcription factor expressed in multiple anterior lineages. Live imaging of ref-2 mutant embryos identified defects in cell division timing and position in anterior lineages. Cis-regulatory dissection identified three ref-2 transcriptional enhancers, one of which is necessary and sufficient for anterior-specific expression. This enhancer is activated by the T-box transcription factors TBX-37 and TBX-38, and surprisingly, concatemerized TBX-37/38 binding sites are sufficient to drive anterior-biased expression in a pop-1/TCF-dependent manner. Taken together, our results demonstrate that TCF can regulate an early-expressed anterior-biased gene in the C. elegans embryo through the binding site of another transcription factor.

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Additional Files

Table_1_strain_list_20220412.xlsx (12 kB)
Table_2_Bacterial_Strain_List.xlsx (8 kB)
Table_3_Quantitative_analyses_raw_data_20220120.xlsx (790 kB)
Table_4_Anterior_genes_summary_data.xlsx (28 kB)
Table_5_Recombinant_DNA_Table.xlsx (11 kB)
Figure_8.pdf (4120 kB)

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