The role of endoglin during mesoderm specification

Abstract

Embryogenesis requires spatiotemporally regulated cellular signals and gene expressions that influence lineage specification, progenitor patterning, and morphogenesis. However the molecular mechanisms that explain how the progenitors commit into different lineages are still poorly understood. Endoglin (ENG) is an ancillary receptor for transforming growth factor-beta (TGF-β) and lack of ENG leads impaired hematopoiesis, cardiac defects and embryonic lethality. Considering the fact that certain mesodermal population can give rise to both cardiac and hematopoietic cells, it indicates that endoglin may play a role in these cell types. Thereby during my predoctoral training, I have aimed to elucidate how endoglin regulates the cell fate choice that results in the specification of early mesodermal precursors into the cardiac or hematopoietic cells. In Chaper 2, I demonstrate that ENG promotes the commitment of early mesodermal progenitors to the hematopoietic lineage at the expense of the cardiac cell fate and ENG-mediated hematopoietic commitment occurs through BMP signaling pathway. In Chapter 3, I illustrate the mechanistic insights how ENG, through activation of BMP and WNT signals, regulates the cell fate decision to secure mesoderm commitment towards the hematopoietic lineage. These studies will uncover a novel role of ENG as a potential mediator between BMP and WNT signaling during mesoderm specification and contribute to broaden our understanding of TGF-β signaling in cell fate decision.