PUBLICATION
miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration
- Authors
- Staton, A.A., Knaut, H., and Giraldez, A.J.
- ID
- ZDB-PUB-110131-6
- Date
- 2011
- Source
- Nature Genetics 43(3): 204-211 (Journal)
- Registered Authors
- Giraldez, Antonio, Knaut, Holger, Staton, Alison
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Movement/genetics*
- Chemokine CXCL12/genetics*
- Chemokine CXCL12/metabolism
- Gene Expression Regulation
- Germ Cells/physiology*
- MicroRNAs/physiology
- Models, Biological
- Receptors, CXCR/genetics
- Receptors, CXCR/metabolism
- Signal Transduction/genetics
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 21258340 Full text @ Nat. Genet.
Citation
Staton, A.A., Knaut, H., and Giraldez, A.J. (2011) miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration. Nature Genetics. 43(3):204-211.
Abstract
microRNAs (miRNAs) function as genetic rheostats to control gene output. Based on their role as modulators, it has been postulated that miRNAs canalize development and provide genetic robustness. Here, we uncover a previously unidentified regulatory layer of chemokine signaling by miRNAs that confers genetic robustness on primordial germ cell (PGC) migration. In zebrafish, PGCs are guided to the gonad by the ligand Sdf1a, which is regulated by the sequestration receptor Cxcr7b. We find that miR-430 regulates sdf1a and cxcr7 mRNAs. Using target protectors, we demonstrate that miR-430-mediated regulation of endogenous sdf1a (also known as cxcl12a) and cxcr7b (i) facilitates dynamic expression of sdf1a by clearing its mRNA from previous expression domains, (ii) modulates the levels of the decoy receptor Cxcr7b to avoid excessive depletion of Sdf1a and (iii) buffers against variation in gene dosage of chemokine signaling components to ensure accurate PGC migration. Our results indicate that losing miRNA-mediated regulation can expose otherwise buffered genetic lesions leading to developmental defects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping