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Hapln1b , a central organizer of the ECM, modulates kit signaling to control developmental hematopoiesis in zebrafish

Monteiro, Rui
Savvides, Savvas N.
Published in Blood advances. 2021, vol. 5, no. 23, p. 4935-4948
Abstract Abstract

During early vertebrate development, hematopoietic stem and progenitor cells (HSPCs) are produced in hemogenic endothelium located in the dorsal aorta, before they migrate to a transient niche where they expand to the fetal liver and the caudal hematopoietic tissue, in mammals and zebrafish, respectively. In zebrafish, previous studies have shown that the extracellular matrix (ECM) around the aorta must be degraded to enable HSPCs to leave the aortic floor and reach blood circulation. However, the role of the ECM components in HSPC specification has never been addressed. In this study, hapln1b, a key component of the ECM, was 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 necessary, at the correct level, to specify HSPCs in the hemogenic endothelium. Furthermore, the expression of hapln1b was necessary to maintain the integrity of the ECM through its link domain. By combining functional analyses and computer modeling, we showed that kitlgb interacts with the ECM to specify HSPCs. The findings show that the ECM is an integral component of the microenvironment and mediates the cytokine signaling that is necessary for HSPC specification.

PMID: 34543380
PMCID: PMC9152995
Full text
Research group Développement du système hémato-vasculaire chez les vertébrés (920)
Swiss National Science Foundation: 310030_184814
(ISO format)
MAHONY, Christopher et al. Hapln1b , a central organizer of the ECM, modulates kit signaling to control developmental hematopoiesis in zebrafish. In: Blood advances, 2021, vol. 5, n° 23, p. 4935-4948. doi: 10.1182/bloodadvances.2020001524 https://archive-ouverte.unige.ch/unige:163371

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Deposited on : 2022-09-20

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