Transcriptional regulation of Eomesodermin and its roles in cell fate allocation during early mouse development

Thesis

Early embryonic development is governed by a tightly regulated series of cell fate decisions to form an entire organism. Eomesodermin (Eomes) is a T-box transcription factor dynamically expressed in the extra-embryonic ectoderm, anterior-visceral endoderm (AVE) and primitive streak during mouse gastrulation. Previous work from our lab shows that Eomes is essential within the AVE for establishment of the anterior-posterior (A-P) axis and within the primitive streak for epithelial-to-mesenchymal transition, and specification of cardiac mesoderm and definitive endoderm. However, the cis-acting regulatory elements that control the critical spatiotemporal expression domains of Eomes are not fully understood. Also, whether Eomes plays a functional role in specification of other mesodermal lineages is unknown. Here, I demonstrate an essential enhancer 8kb downstream from the TSS is necessary and sufficient for the correct expression of Eomes in the AVE and primitive streak. Mutants harboring a deletion of this enhancer exhibit A-P patterning defects and derivatives of the anterior primitive streak are compromised. The discovery of this essential enhancer provides greater understanding into how this critical gene is regulated during development. Moreover, this is the first characterisation of an Eomes enhancer that drives AVE expression. Additionally, I show that Eomes is required for the specification of haematopoietic mesoderm. Thus, implicating Eomes as a central player in the allocation of multiple cell fates within the primitive streak.

Authors: Simon, C

• DOI: 10.5287/ora-9o59nwvzo
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Gastrulation; Haematopoeisis; Primitive streak; Enhancer; Eomes; Definitive endoderm
• Subjects: Developmental biology