title: Regulation of murine normal and stress-induced erythropoiesis by Desert Hedgehog.
abstract: The function of Hedgehog signaling in hematopoiesis is controversial, with different experimental systems giving opposing results. Here we examined the role of Desert Hedgehog (Dhh) in the regulation of murine erythropoiesis. Dhh is one of 3 mammalian Hedgehog family proteins. Dhh is essential for testis development and Schwann cell function. We show, by analysis of Dhh-deficient mice, that Dhh negatively regulates multiple stages of erythrocyte differentiation. In Dhh-deficient bone marrow, the common myeloid progenitor (CMP) population was increased, but differentiation from CMP to granulocyte/macrophage progenitor was decreased, and the mature granulocyte population was decreased, compared with wild-type (WT). In contrast, differentiation from CMP to megakaryocyte/erythrocyte progenitor was increased, and the megakaryocyte/erythrocyte progenitor population was increased. In addition, we found that erythroblast populations were Dhh-responsive in vitro and ex vivo and that Dhh negatively regulated erythroblast differentiation. In Dhh-deficient spleen and bone marrow, BFU-Es and erythroblast populations were increased compared with WT. During recovery of hematopoiesis after irradiation, and under conditions of stress-induced erythropoiesis, erythrocyte differentiation was accelerated in both spleen and bone marrow of Dhh-deficient mice compared with WT.
authors.affiliation: Immunobiology Unit, University College London Institute of Child Health, 30 Guilford St., London, United Kingdom.
authors.forename: Ching-in
authors.initials: CI
authors.lastname: Lau
authors.forename: Susan V
authors.initials: SV
authors.lastname: Outram
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Saldaña
authors.forename: Anna L
authors.initials: AL
authors.lastname: Furmanski
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Dessens
authors.forename: Tessa
authors.initials: T
authors.lastname: Crompton
mesh_terms: D000367:Age Factors; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000528:radiation effects; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D004900:Erythroblasts / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D004920:Erythropoiesis / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D013154:Spleen / Q000378:metabolism / Q000528:radiation effects; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D014916:Whole-Body Irradiation
chemical_list: D053823:Hedgehog Proteins