Hematopoietic defects in rps29 mutant zebrafish depend upon p53 activation
- Authors
- Taylor, A.M., Humphries, J.M., White, R.M., Murphey, R.D., Burns, C.E., and Zon, L.I.
- ID
- ZDB-PUB-111130-7
- Date
- 2012
- Source
- Experimental hematology 40(3): 228-237 (Journal)
- Registered Authors
- Burns (Erter), Caroline, Taylor, Alison, White, Richard M., Zon, Leonard I.
- Keywords
- Diamond Blackfan anemia, hematopoietic stem cells, ribosomal proteins
- MeSH Terms
-
- Cell Cycle/genetics
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/physiology*
- Nervous System/embryology
- Genes, p53
- Apoptosis/genetics
- Gene Expression Profiling
- Disease Models, Animal
- Hematopoietic Stem Cells/cytology
- Hematopoietic Stem Cells/metabolism
- Ribosomal Proteins/genetics
- Ribosomal Proteins/physiology*
- Animals
- Bone and Bones/embryology
- Erythropoiesis/genetics
- Hematopoiesis/genetics*
- DNA Damage
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- Mutation
- Anemia, Diamond-Blackfan/genetics
- Transcription Factors/biosynthesis
- Transcription Factors/genetics
- Oligonucleotide Array Sequence Analysis
- Morphogenesis/genetics
- Zebrafish/embryology
- Zebrafish/genetics*
- Gene Expression Regulation, Developmental/radiation effects
- Genes, Lethal
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/pathology
- Embryo, Nonmammalian/radiation effects
- Gene Knockdown Techniques
- PubMed
- 22120640 Full text @ Exp. Hematol.
Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Blackfan anemia (DBA), a rare congenital disease characterized by red cell aplasia and distinctive craniofacial anomalies. A zebrafish screen uncovered decreased hematopoietic stem cells (HSCs) in embryos with mutations in ribosomal protein rps29. Here, we determined that rps29-/- embryos also have red blood cell defects and increased apoptosis in the head. As the p53 pathway has been shown to play a role in other ribosomal protein mutants, we studied the genetic relationship of rps29 and p53. Transcriptional profiling revealed that genes up-regulated in the rps29 mutant are enriched for genes up-regulated by p53 after irradiation. p53 mutation near completely rescues the rps29 morphological and hematopoietic phenotypes, demonstrating that p53 mediates the effects of rps29 knockdown. We also identified neuronal gene orthopedia protein a (otpa) as one whose expression correlates with rps29 expression, suggesting that levels of expression of some genes are dependent on rps29 levels. Together, our studies demonstrate a role of p53 in mediating the cellular defects associated with rps29 and establish a role for rps29 and p53 in HSCs and red blood cell development.