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Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells
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Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells
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Journal Article
Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells
2016
Overview
During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta–gonad–mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of
ex vivo
and
in vivo
approaches, we report here that stage-specific reciprocal dorso–ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs.
It is unclear how the microenvironment of the aorta-gonad-mesonephros influences haematopoietic stem cell (HSC) production early in mouse development. Here, Souilhol
et al.
use an
in vitro
aggregate system as a tool to understand how several pathways, BMP, SCF and Shh, may regulate HSC production.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 13/106
/ 13/107
/ 13/21
/ 13/31
/ 14
/ 14/19
/ Animals
/ Bone Morphogenetic Protein 4 - genetics
/ Bone Morphogenetic Protein 4 - metabolism
/ Female
/ Hedgehog Proteins - genetics
/ Hedgehog Proteins - metabolism
/ Hematopoietic Stem Cell Transplantation
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - metabolism
/ Humanities and Social Sciences
/ Male
/ Science
