PUBLICATION

Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal protein paralogs

Authors
Zhang, Y., Duc, A.C., Rao, S., Sun, X.L., Bilbee, A.N., Rhodes, M., Li, Q., Kappes, D.J., Rhodes, J., and Wiest, D.L.
ID
ZDB-PUB-130312-35
Date
2013
Source
Developmental Cell   24(4): 411-425 (Journal)
Registered Authors
Li, Qin, Rhodes, Jennifer, Wiest, David
Keywords
none
MeSH Terms
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism
  • Core Binding Factor Alpha 2 Subunit/metabolism
  • Gene Expression Regulation, Developmental*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction
  • Blotting, Western
  • Smad1 Protein/metabolism
  • T-Lymphocytes/cytology*
  • T-Lymphocytes/metabolism
  • Cell Differentiation
  • RNA, Messenger/genetics
  • Cell Lineage*
  • Animals
  • Ribosomal Proteins/genetics
  • Ribosomal Proteins/metabolism*
  • Ribosomes/metabolism
  • Thymus Gland/cytology
  • Thymus Gland/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
(all 24)
PubMed
23449473 Full text @ Dev. Cell
Abstract

It remains controversial whether the highly homologous ribosomal protein (RP) paralogs found in lower eukaryotes have distinct functions and this has not been explored in vertebrates. Here we demonstrate that despite ubiquitous expression, the RP paralogs, Rpl22 and Rpl22-like1 (Rpl22l1) play essential, distinct, and antagonistic roles in hematopoietic development. Knockdown of Rpl22 in zebrafish embryos selectively blocks the development of T lineage progenitors after they have seeded the thymus. In contrast, knockdown of the Rpl22 paralog, Rpl22l1, impairs the emergence of hematopoietic stem cells (HSC) in the aorta-gonad-mesonephros by abrogating Smad1 expression and the consequent induction of essential transcriptional regulator, Runx1. Indeed, despite the ability of both paralogs to bind smad1 RNA, Rpl22 and Rpl22l1 have opposing effects on Smad1 expression. Accordingly, circumstances that tip the balance of these paralogs in favor of Rpl22 (e.g., Rpl22l1 knockdown or Rpl22 overexpression) result in repression of Smad1 and blockade of HSC emergence.

Genes / Markers
Figures
Figure Gallery (13 images) / 2
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cz2TgTransgenic Insertion
    f1TgTransgenic Insertion
      fr101TgTransgenic Insertion
        la2TgTransgenic Insertion
          sd2TgTransgenic Insertion
            uwm1TgTransgenic Insertion
              y1TgTransgenic Insertion
                zdf1
                  Point Mutation
                  zdf8TgTransgenic Insertion
                    1 - 9 of 9
                    Show
                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Target Reagent Reagent Type
                    rpl22MO1-rpl22MRPHLNO
                    rpl22l1MO1-rpl22l1MRPHLNO
                    1 - 2 of 2
                    Show
                    Fish
                    Antibodies
                    Name Type Antigen Genes Isotypes Host Organism
                    Ab1-rpl22l1polyclonal
                      IgGRabbit
                      Ab1-smadpolyclonalIgGRabbit
                      Ab1-smad1polyclonalIgGRabbit
                      Ab2-smadpolyclonal
                        Rabbit
                        1 - 4 of 4
                        Show
                        Orthology
                        Gene Orthology
                        rpl22
                        rpl22l1
                        1 - 2 of 2
                        Show
                        Engineered Foreign Genes
                        Marker Marker Type Name
                        DsRedEFGDsRed
                        EGFPEFGEGFP
                        GFPEFGGFP
                        1 - 3 of 3
                        Show
                        Mapping
                        No data available