PUBLICATION
Smad1 and Smad5 differentially regulate embryonic hematopoiesis
- Authors
- McReynolds, L.J., Gupta, S., Figueroa, M.E., Mullins, M.C., and Evans, T.
- ID
- ZDB-PUB-070907-21
- Date
- 2007
- Source
- Blood 110(12): 3881-3890 (Journal)
- Registered Authors
- Evans, Todd, Mullins, Mary C.
- Keywords
- none
- Datasets
- GEO:GSE8903
- MeSH Terms
-
- Zebrafish/embryology*
- Zebrafish/genetics
- Metalloproteins/biosynthesis
- Metalloproteins/genetics
- Bone Morphogenetic Proteins/genetics
- Bone Morphogenetic Proteins/metabolism
- Gene Expression Profiling
- Gene Expression Regulation, Developmental/physiology*
- Basic Helix-Loop-Helix Transcription Factors/biosynthesis
- Basic Helix-Loop-Helix Transcription Factors/genetics
- DNA-Binding Proteins/biosynthesis
- DNA-Binding Proteins/genetics
- Oligonucleotide Array Sequence Analysis
- Hematopoietic Stem Cells/cytology
- Hematopoietic Stem Cells/metabolism*
- Smad1 Protein/genetics
- Smad1 Protein/metabolism*
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Macrophages/cytology
- Macrophages/metabolism
- Smad5 Protein/genetics
- Smad5 Protein/metabolism*
- Hematopoiesis/physiology*
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- Proto-Oncogene Proteins/biosynthesis
- Proto-Oncogene Proteins/genetics
- Transcription Factors
- Animals
- Signal Transduction/physiology
- LIM Domain Proteins
- Erythrocytes/cytology
- Erythrocytes/metabolism
- PubMed
- 17761518 Full text @ Blood
Citation
McReynolds, L.J., Gupta, S., Figueroa, M.E., Mullins, M.C., and Evans, T. (2007) Smad1 and Smad5 differentially regulate embryonic hematopoiesis. Blood. 110(12):3881-3890.
Abstract
The 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 function 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 two highly related proteins have inherently distinct activities. Microarray experiments revealed that the two proteins regulate redundantly 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping