期刊
DEVELOPMENT
卷 136, 期 15, 页码 2613-2621出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.034728
关键词
AGM; Hematopoiesis; Hedgehog; Gut; Mouse embryo; Positional information
资金
- NIH [R37 DK5107]
- NWO VICI [916.36.601]
- Netherlands BSIK Award [03038]
- KWF Dutch Cancer Society [2001-2442]
- HFSP [RG0345/1999]
- Medical Research Council [G0300723B, G0800784, G0800784B, MC_U137970202] Funding Source: researchfish
- MRC [G0800784, MC_U137970202] Funding Source: UKRI
Hematopoiesis is initiated in several distinct tissues in the mouse conceptus. The aorta-gonad-mesonephros (AGM) region is of particular interest, as it autonomously generates the first adult type hematopoietic stem cells (HSCs). The ventral position of hematopoietic clusters closely associated with the aorta of most vertebrate embryos suggests a polarity in the specification of AGM HSCs. Since positional information plays an important role in the embryonic development of several tissue systems, we tested whether AGM HSC induction is influenced by the surrounding dorsal and ventral tissues. Our explant culture results at early and late embryonic day 10 show that ventral tissues induce and increase AGM HSC activity, whereas dorsal tissues decrease it. Chimeric explant cultures with genetically distinguishable AGM and ventral tissues show that the increase in HSC activity is not from ventral tissue-derived HSCs, precursors or primordial germ cells (as was previously suggested). Rather, it is due to instructive signaling from ventral tissues. Furthermore, we identify Hedgehog protein(s) as an HSC inducing signal.
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