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
  • Models, Biological
  • Recombinant Proteins/genetics
  • Recombinant Proteins/metabolism
  • Gene Expression Regulation, Developmental*
  • Forkhead Transcription Factors/genetics*
  • Embryo, Nonmammalian
  • Enhancer Elements, Genetic
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Animals
  • Organ Specificity/genetics
  • Animals, Genetically Modified
  • Lymphoid Enhancer-Binding Factor 1/metabolism
  • Lymphoid Enhancer-Binding Factor 1/physiology*
  • Protein Binding
  • Tissue Distribution
  • Central Nervous System/embryology*
  • Central Nervous System/metabolism*
  • Zebrafish Proteins/genetics*
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
(all 21)
PubMed
18950487 Full text @ BMC Dev. Biol.
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
Figures
Figure Gallery (8 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
e1TgTransgenic Insertion
    knu3TgTransgenic Insertion
      w26TgTransgenic Insertion
        x8
          		Deficiency
          zc41TgTransgenic Insertion
            zc42TgTransgenic Insertion
              zc44TgTransgenic Insertion
                zc46TgTransgenic Insertion
                  zc47TgTransgenic Insertion
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Target Reagent Reagent Type
                    lef1MO2-lef1MRPHLNO
                    1 - 1 of 1
                    Show
                    Fish
                    Fish
                    Df(Chr01:lef1,msxb)x8/x8
                    e1Tg
                    e1Tg + MO2-lef1
                    knu3Tg
                    knu3Tg + MO2-lef1
                    w26Tg
                    WT
                    WT + MO2-lef1
                    zc41Tg
                    zc41Tg + MO2-lef1
                    1 - 10 of 16
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                    Antibodies
                    No data available
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    EGFPEFGEGFP
                    GFPEFGGFP
                    1 - 2 of 2
                    Show
                    Mapping
                    No data available
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                    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.