Plxnc1 promotes the development of hematopoietic stem and progenitor cells by regulating Rac1-dependent Wnt signaling and DHA Synthesis

Although many intrinsic regulators of EHT have been identified, how niche-derived cues are integrated with intracellular signaling and metabolic programs to control HSPCs emergence remains incompletely understood.

Here, we identify Plxnc1, a Plexin family receptor specifically enriched in HECs, is essential for HECs specification and definitive HSPCs production in zebrafish. Loss of Plxnc1 impairs definitive hematopoiesis without affecting primitive hematopoiesis or vascular development. Mechanistically, endothelial-derived Sema7a activates Plxnc1 in HECs, leading to Rac1 activation and sustained canonical Wnt/β-catenin signaling.