Figure 8. Loss of YY1 leads to defects in paracrine signals necessary for angiogenesis and visceral endoderm integrity.

A, B) A summary of the signaling events downstream of YY1 in WT and mutant yolk sacs. A) In the presence of YY1, normal VEGF levels produced by the visceral endoderm (VE) allow the underlying mesoderm derivatives (ME) to undergo events associated with vascular remodeling. The underlying vascular tissue is the source of a VEGF-dependant paracrine signal(s) that is required by the visceral endoderm to maintain characteristics such as epithelial polarity, large apical lysosomes and HNF4α expression. B) In the absence of YY1 in the visceral endoderm, decreased levels of paracrine VEGF result in defective angiogenesis, increased apoptosis and decreased proliferation in the adjacent mesoderm. Because of reduced VEGF signaling, the yolk sac mesoderm does not generate the paracrine signal(s) needed to maintain epithelial characteristics in the visceral endoderm, resulting in decreased HNF4α, a loss of large lysosomes and reduced CDH1 levels.