Prdm14 acts upstream of islet2 transcription to regulate axon growth of primary motoneurons in zebrafish
- Authors
- Liu, C., Ma, W., Su, W., and Zhang, J.
- ID
- ZDB-PUB-121127-3
- Date
- 2012
- Source
- Development (Cambridge, England) 139(24): 4591-4600 (Journal)
- Registered Authors
- Liu, Chao, Ma, Weirui, Zhang, Jian
- Keywords
- Prdm14, zebrafish, motoneuron, axon outgrowth, Islet2
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Axons/metabolism
- Axons/physiology*
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/genetics
- Gene Expression Regulation, Developmental/physiology
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- LIM-Homeodomain Proteins/genetics*
- LIM-Homeodomain Proteins/metabolism
- LIM-Homeodomain Proteins/physiology
- Motor Neurons/metabolism
- Motor Neurons/physiology*
- Nerve Net/embryology
- Nerve Net/metabolism
- Repressor Proteins/genetics
- Repressor Proteins/metabolism
- Repressor Proteins/physiology*
- Signal Transduction/genetics
- Trans-Activators/genetics
- Trans-Activators/metabolism
- Trans-Activators/physiology*
- Transcription Factors/genetics*
- Transcription Factors/metabolism
- Transcription Factors/physiology
- Transcription, Genetic/genetics
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/physiology
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Zebrafish Proteins/physiology*
- PubMed
- 23136389 Full text @ Development
The precise formation of three-dimensional motor circuits is essential for movement control. Within these circuits, motoneurons (MNs) are specified from spinal progenitors by dorsoventral signals and distinct transcriptional programs. Different MN subpopulations have stereotypic cell body positions and show specific spatial axon trajectories. Our knowledge of MN axon outgrowth remains incomplete. Here, we report a zebrafish gene-trap mutant, short lightning (slg), in which prdm14 expression is disrupted. slg mutant embryos show shortened axons in caudal primary (CaP) MNs resulting in defective embryonic movement. Both the CaP neuronal defects and behavior abnormality of the mutants can be phenocopied by injection of a prdm14 morpholino into wild-type embryos. By removing a copy of the inserted transposon from homozygous mutants, prdm14 expression and normal embryonic movement were restored, confirming that loss of prdm14 expression accounts for the observed defects. Mechanistically, Prdm14 protein binds to the promoter region of islet2, a known transcription factor required for CaP development. Notably, disruption of islet2 function caused similar CaP axon outgrowth defects as observed in slg mutant embryos. Furthermore, overexpression of islet2 in slg mutant embryos rescued the shortened CaP axon phenotypes. Together, these data reveal that prdm14 regulates CaP axon outgrowth through activation of islet2 expression.