PUBLICATION
Domain-specific regulation of foxP2 CNS expression by lef1
- Authors
- Bonkowsky, J.L., Wang, X., Fujimoto, E., Lee, J.E., Chien, C.B., and Dorsky, R.I.
- ID
- ZDB-PUB-091030-2
- Date
- 2008
- Source
- BMC Developmental Biology 8: 103 (Journal)
- Registered Authors
- Bonkowsky, Joshua, Chien, Chi-Bin, Dorsky, Richard, Fujimoto, Esther, Lee, Ji Eun, Wang, Xu
- Keywords
- none
- MeSH Terms
-
- Enhancer Elements, Genetic
- Forkhead Transcription Factors/genetics*
- Animals
- Models, Biological
- Lymphoid Enhancer-Binding Factor 1/metabolism
- Lymphoid Enhancer-Binding Factor 1/physiology*
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Central Nervous System/embryology*
- Central Nervous System/metabolism*
- Recombinant Proteins/genetics
- Recombinant Proteins/metabolism
- Tissue Distribution
- Zebrafish Proteins/genetics*
- Gene Expression Regulation, Developmental*
- Organ Specificity/genetics
- Animals, Genetically Modified
- Zebrafish/embryology
- Zebrafish/genetics
- Embryo, Nonmammalian
- Protein Binding
- PubMed
- 18950487 Full text @ BMC Dev. Biol.
Citation
Bonkowsky, J.L., Wang, X., Fujimoto, E., Lee, J.E., Chien, C.B., and Dorsky, R.I. (2008) Domain-specific regulation of foxP2 CNS expression by lef1. BMC Developmental Biology. 8:103.
Abstract
BACKGROUND: FOXP2 is a forkhead transcription factor critical for normal development of language in humans, but little is known of its broader function and regulation during central nervous system (CNS) development. We report here that lef1, a member of the Lef/Tcf family of transcription factors activated by Wnt signaling, regulates foxP2 during embryogenesis, and we isolate novel foxP2 enhancers which are lef1-dependent. RESULTS: Loss, knock down, or inhibition of lef1 led to loss of foxP2 expression. We isolated DNA fragments from the foxP2 genomic region that function as enhancers to drive GFP expression in the CNS during development, including in the telencephalon, diencephalon, eye, tectum, and hindbrain. Three of these enhancers, foxP2-enhancerA.1, foxP2-enhancerB, and foxP2-enhancerD, contain putative Lef1 binding sites, and are regulated by lef1. However, two other genomic fragments containing Lef1 sites failed to function in vivo as enhancers. Chromatin immunoprecipitation confirmed that Lef1 binds to sites in foxP2-enhancerA.1 and foxP2-enhancerB. CONCLUSION: This work shows that lef1 is necessary for expression of foxP2 in the tectum, mid-hindbrain boundary, and hindbrain during CNS development, and is the first insight into the upstream regulation of foxP2 during development. We also demonstrate that in silico prediction of potential lef1 binding sites poorly predicts their ability to function in vivo as enhancers. The foxP2 enhancers we identified will allow dissection of foxP2's role during CNS development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping