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First published online 1 July 2009
doi: 10.1242/dev.034728

Development 136, 2613-2621 (2009)
Published by The Company of Biologists 2009
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Ventral embryonic tissues and Hedgehog proteins induce early AGM hematopoietic stem cell development

Marian Peeters1, Katrin Ottersbach2, Karine Bollerot1, Claudia Orelio1, Marella de Bruijn3, Mark Wijgerde4 and Elaine Dzierzak1,*

1 Erasmus Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
2 Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
3 Weatherall Institute for Molecular Medicine, Molecular Haematology Unit, Oxford University, Oxford OX3 9DS, UK.
4 Department of Reproduction and Development, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.

* Author for correspondence (e-mail: e.dzierzak{at}erasmusmc.nl)

Accepted 21 May 2009

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.

Key words: AGM, Hematopoiesis, Hedgehog, Gut, Mouse embryo, Positional information


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Hedgehog: haematopoietic stem cell inducer?

Development 2009 136: e1504. [Full Text]  





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