The roles of BMP and IL-3 signaling pathways in the control of hematopoietic stem cells in the mouse embryo

Abstract

During mouse ontogeny, the first adult-type hematopoietic stem cells (HSC) are autonomously generated at mid-gestation in the AGM (Aorta-Gonad-Mesonephros) region. Successively present in different anatomical sites where they will expand, HSCs will finally colonize the bone marrow (BM) where they will reside during the entire adult life. In the bone marrow, both HSC self-renewal and differentiation are controlled at cellular and molecular levels by interactions with the stromal microenvironment. So far, very little is known about the extracellular factors involved in the regulation of embryonic HSC emergence, survival and expansion. In the present review, we outline the BMP and IL-3 signaling pathways that are critical for the growth and potential of embryonic HSCs. We will also discuss how these pathways might be integrated with the ones of Notch and Mpl/thrombopoietin, also identified as important key regulators of AGM HSC activity.

Dpp dependent Hematopoietic stem cells give rise to Hh dependent blood progenitors in larval lymph gland of Drosophila

“…This has a far-reaching implication spilling into stem cell based therapies, wherein it is imperative to know how tissue specific stem cells are specified in development. Furthermore, the transcriptional networks controlling HSC fate during mammalian embryonic development are highly complex (Robin and Durand, 2010). In this direction, the fly model can step in to identify and elucidate not only normal development but also several uncharacterized early pathological events linked with embryonic HSC related disorders.…”

The many faces of hematopoietic stem cell heterogeneity

“…The initiation of HSC generation is tightly controlled by the local microenvironment: the ventral aortic endothelium and/or subaortic mesenchyme express molecules that trigger EHT and subsequent generation of HSCs (Richard et al, 2013; Durand et al, 2007; Pouget et al, 2014; Kaimakis et al, 2013; Robin and Durand, 2010). Of these molecules, BMP is expressed in the ventral aspect of the AGM in mesenchymal and aortic endothelial cells (Durand et al, 2007; Marshall et al, 2000) and has been shown to affect HSC activity in AGM explant cultures (Durand et al, 2007).…”

Aortic remodelling during hemogenesis: is the chicken paradigm unique?

“…Thus the potential to home to this location was conferred by the pre-treatment, and the existence of a second requirement to give rise to hematopoiesis was confirmed despite this second signal was yet to be identified. The BMP family of growth factors is well established as ventralizing factors and was recently demonstrated to be major signalling pathway during the production of HSCs (Durand et al, 2007;Robin and Durand, 2010), yet, pre-treatment of somitic mesoderm with BMP 4 did not confer the ability to home to the aortic floor (Pardanaud and Dieterlen-Lievre, 1999). The paradoxical inefficiency of BMP in this particular set up might be due to a mistimed treatment.…”