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
Keywords
none
MeSH Terms
  • Animals
  • Blotting, Western
  • Cell Differentiation
  • Cell Lineage*
  • Core Binding Factor Alpha 2 Subunit/metabolism
  • Gene Expression Regulation, Developmental*
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism
  • RNA, Messenger/genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribosomal Proteins/genetics
  • Ribosomal Proteins/metabolism*
  • Ribosomes/metabolism
  • Smad1 Protein/metabolism
  • T-Lymphocytes/cytology*
  • T-Lymphocytes/metabolism
  • Thymus Gland/cytology
  • Thymus Gland/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
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
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes