Endothelial cells regulated by RNF20 orchestrate the proliferation and differentiation of neural precursor cells during embryonic development

The intimate communication between the vascular and nervous systems is critical for maintaining central nervous system (CNS) development. However, whether cerebrovascular endothelial cells (ECs) can orchestrate neural precursor cell (NPC) proliferation and differentiation, and the identity of the signals involved therein, is unclear. Here, we find that the development of ECs is often accompanied by DNA damage. RNF20, an E3 ubiquitin ligase, is required for the DNA damage response (DDR). The deletion of RNF20 causes the accumulation of DNA damage in ECs, which fails to secrete cartilage intermediate layer protein 2 (CILP2). Moreover, the loss of endothelium-derived CILP2 alters the downstream cascade signaling of Wnt signaling pathways through the interaction with Wnt3a, which disturbs the NPC fate and causes autism-like behaviors in mice. Therefore, the close and refined controlled neurovascular interactions ensure the normal operation of neurogenesis during embryonic development.