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

摘要

During embryonic development adult haematopoietic stem cells emerge asymmetrically in the ventral niche of the aorta-gonad-mesonephros (AGM) region. However, it is not clear whether inductive interactions are involved in the emergence of haematopoietic stem cells. We report that stage-specific reciprocal dorso-ventral inductive interactions and lateral input from uro-genital ridges are required to drive development of haematopoietic stem cells across the dorso-ventral axis of the dorsal aorta. We show that inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Shh produced dorsally and SCF produced ventrally and laterally as well as ventral BMP inhibitory signalling are integral parts of the epistatic regulatory system that underpins development of haematopoietic stem cells in the dorsal aorta. Complex spatial arrangement of signalling pathways defined here may need to be recapitulated for efficient in vitro generation of haematopoietic stem cells for therapeutic applications.