Hapln1b, a central organizer of the extracellular matrix, modulates kit signalling to control developmental haematopoiesis.

During early vertebrate development, hematopoietic stem and progenitor cells (HSPCs) are produced from hemogenic endothelium located in the dorsal aorta, before they migrate to a transient niche where they expand, the fetal liver and the caudal hematopoietic tissue (CHT), in mammals and zebrafish, respectively. In zebrafish, previous studies have shown that the extracellular matrix (ECM) around the aorta needs to be degraded to allow HSPCs to leave the aortic floor and reach blood circulation. However, the role of the ECM components in HSPC specification has never been addressed. We show here that hapln1b, a key component of the ECM is specifically expressed in hematopoietic sites in the zebrafish embryo. Gain- and loss-of-function experiments all resulted in the absence of HSPCs in the early embryo, showing that hapln1b is required, at the correct level, to specify HSPCs in the hemogenic endothelium. Furthermore, we show that the expression of hapln1b is necessary to maintain the integrity of the ECM through its link domain. By combining functional analyses and computer modelling, we show that kitlgb interacts with the ECM to specify HSPCs. We demonstrate that the ECM is an integral component of the microenvironment and mediates cytokine signalling that is required for HSPC specification.