title: Ventral embryonic tissues and Hedgehog proteins induce early AGM hematopoietic stem cell development.
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.
authors: Erasmus Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Marian
authors: M
authors: Peeters
authors: Katrin
authors: K
authors: Ottersbach
authors: Karine
authors: K
authors: Bollerot
authors: Claudia
authors: C
authors: Orelio
authors: Marella
authors: M
authors: de Bruijn
authors: Mark
authors: M
authors: Wijgerde
authors: Elaine
authors: E
authors: Dzierzak
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000378:metabolism; D002449:Cell Aggregation; D002452:Cell Count; D046528:Chimerism; D003114:Colony-Forming Units Assay; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D006066:Gonads / Q000166:cytology* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008650:Mesonephros / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins