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Blood, 1 December 2007, Vol. 110, No. 12, pp. 3881-3890. Prepublished online as a Blood First Edition Paper on August 29, 2007; DOI 10.1182/blood-2007-04-085753. This Article Full Text Full Text (PDF) Supplemental Methods and Tables All Versions of this Article: blood-2007-04-085753v1 110/12/3881    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by McReynolds, L. J. Articles by Evans, T. Search for Related Content PubMed PubMed Citation Articles by McReynolds, L. J. Articles by Evans, T. Related Collections Hematopoiesis and Stem Cells Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Smad1 and Smad5 differentially regulate embryonic hematopoiesis Lisa J. McReynolds1, Sunny Gupta1, Maria E. Figueroa1, Mary C. Mullins2, and Todd Evans1 1 Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY; and 2 Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia The bone morphogenetic protein (BMP) signaling pathway regulates multiple steps of hematopoiesis, mediated through receptor-regulated Smads, including Smad1 and Smad5. Here, we use loss-of-function approaches in zebrafish to compare the roles of Smad1 and Smad5 during embryonic hematopoiesis. We show that knockdown of Smad1 or Smad5 generates distinct and even opposite hematopoietic phenotypes. Embryos depleted for Smad1 have an increased number of primitive erythrocytes, but fail to produce mature embryonic macrophages. In contrast, Smad5-depleted embryos are defective in primitive erythropoiesis, yet have normal numbers of macrophages. Loss of either Smad1 or Smad5 causes a failure in the generation of definitive hematopoietic progenitors. To investigate the mechanism behind these phenotypes, we used rescue experiments and found that Smad5 is unable to rescue the Smad1 loss-of-function phenotype, indicating that the 2 highly related proteins have inherently distinct activities. Microarray experiments revealed that the 2 proteins redundantly regulate the key initiators of the hemato-vascular program, including scl, lmo2, and gfi1. However, each also regulates a remarkably distinct genetic program, with Smad5 uniquely regulating the BMP signaling pathway itself. Our results suggest that specificity of BMP signaling output, with respect to hematopoiesis, can be explained by differential functions of Smad1 and Smad5. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Tao, Y. Cai, and K. Sampath The Integrator subunits function in hematopoiesis by modulating Smad/BMP signaling Development, August 15, 2009; 136(16): 2757 - 2765. [Abstract] [Full Text] [PDF] F. Lohmann and J. J. Bieker Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment Development, June 15, 2008; 135(12): 2071 - 2082. [Abstract] [Full Text] [PDF]

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