title: Signaling from the sympathetic nervous system regulates hematopoietic stem cell emergence during embryogenesis.
abstract: The first adult-repopulating hematopoietic stem cells (HSCs) emerge in the aorta-gonads-mesonephros (AGM) region of the embryo. We have recently identified the transcription factor Gata3 as being upregulated in this tissue specifically at the time of HSC emergence. We now demonstrate that the production of functional and phenotypic HSCs in the AGM is impaired in the absence of Gata3. Furthermore, we show that this effect on HSC generation is secondary to the role of Gata3 in the production of catecholamines, the mediators of the sympathetic nervous system (SNS), thus making these molecules key components of the AGM HSC niche. These findings demonstrate that the recently described functional interplay between the hematopoietic system and the SNS extends to the earliest stages of their codevelopment and highlight the fact that HSC development needs to be viewed in the context of the development of other organs.
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0XY, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Fitch
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Kimber
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Wilson
authors.forename: Aimée
authors.initials: A
authors.lastname: Parker
authors.forename: Bahar
authors.initials: B
authors.lastname: Mirshekar-Syahkal
authors.forename: Berthold
authors.initials: B
authors.lastname: Göttgens
authors.forename: Alexander
authors.initials: A
authors.lastname: Medvinsky
authors.forename: Elaine
authors.initials: E
authors.lastname: Dzierzak
authors.forename: Katrin
authors.initials: K
authors.lastname: Ottersbach
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000196:embryology; D002395:Catecholamines / Q000378:metabolism*; D002460:Cell Line; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000502:physiology; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000196:embryology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008650:Mesonephros / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D055153:Stem Cell Niche; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse