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Ventral embryonic tissues and Hedgehog proteins induce early AGM hematopoietic stem cell development.

TitleVentral embryonic tissues and Hedgehog proteins induce early AGM hematopoietic stem cell development.
Publication TypeJournal Article
Year of Publication2009
AuthorsPeeters M, Ottersbach K, Bollerot K, Orelio C, de Bruijn M, Wijgerde M, Dzierzak E
JournalDevelopment
Volume136
Issue15
Pagination2613-21
Date Published2009 Aug
ISSN0950-1991
KeywordsAnimals, Aorta, Cell Aggregation, Cell Count, Chimerism, Colony-Forming Units Assay, Embryo, Mammalian, Gonads, Hedgehog Proteins, Hematopoietic Stem Cells, Mesonephros, Mice, Signal Transduction
Abstract

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.

DOI10.1242/dev.034728
Alternate JournalDevelopment
PubMed ID19570846
PubMed Central IDPMC2709067
Grant ListG0800784 / / Medical Research Council / United Kingdom
MC_U137970202 / / Medical Research Council / United Kingdom
R37 DK054077 / DK / NIDDK NIH HHS / United States
R37 DK054077-09 / DK / NIDDK NIH HHS / United States
R37 DK51077 / DK / NIDDK NIH HHS / United States
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