Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells

Céline Souilhol, Christèle Gonneau, Javier G. Lendinez, Antoniana Batsivari, Stanislav Rybtsov, Heather Wilson, Lucia Morgado-Palacin, David Hills, Samir Taoudi, Jennifer Antonchuk, Suling Zhao, Alexander Medvinsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number10784
Number of pages13
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 8 Mar 2016

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