BMP4 and Madh5 regulate the erythroid response to acute anemia.
Acute anemia initiates a systemic response that results in the rapid mobilization and differentiation of erythroid progenitors in the adult spleen. The flexed-tail (f) mutant mice exhibit normal steady-state erythropoiesis but are unable to rapidly respond to acute erythropoietic stress. Here, we show that f/f mutant mice have a mutation in Madh5. Our analysis shows that BMP4/Madh5-dependent signaling, regulated by hypoxia, initiates the differentiation and expansion of erythroid progenitors in the spleen. These findings suggest a new model where stress erythroid progenitors, resident in the spleen, are poised to respond to changes in the microenvironment induced by acute anemia.
Lenox
Laurie E
LE
Department of Veterinary Science, Graduate Program in Biochemistry, Microbiology and Molecular Biology, and Huck Institute for Life Sciences Cell and Developmental Biology Option, Pennsylvania State University, University Park, PA 16802, USA.
Perry
John M
JM
Paulson
Robert F
RF
D000208:Acute Disease; D000483:Alleles; D000740:Anemia / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D004920:Erythropoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051902:Smad5 Protein; D013154:Spleen / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D051902:Smad5 Protein; C497798:Smad5 protein, mouse; D015534:Trans-Activators