Working model on the role of Zeb2 in HSC/HPC biology. (A) Top panel depicts the wild-type situation in which Zeb2 expression in the HSCs/HPCs of the fetal liver simultaneously regulates their differentiation potential and plays a key role in their proper adhesion/localization and mobility. Zeb2 expression in HSCs/HPCs allows them to enter the circulation and provide the necessary angiogenic factors, including Ang1, essential for pericyte recruitment and vessel stability. (B) Bottom panel depicts the situation on hematopoietic-specific loss of Zeb2 expression. Zeb2-null fetal liver HSCs/HPCs are blocked in their differentiation potential and show increased adhesion that is correlated with increased Cxcr4 and integrin β1 expression. This results in immobility/retention of HSCs/HPCs in the fetal liver, preventing them from reentering the circulation, which subsequently results in a systemic decrease of essential angiogenic factors, including Ang1, and a loss of pericyte coverage of the head vessels and subsequent vessel leakage.