PUBLICATION

Lef1-dependent hypothalamic neurogenesis inhibits anxiety

Authors
Xie, Y., Kaufmann, D., Moulton, M.J., Panahi, S., Gaynes, J.A., Watters, H.N., Zhou, D., Xue, H.H., Fung, C.M., Levine, E.M., Letsou, A., Brennan, K.C., Dorsky, R.I.
ID
ZDB-PUB-170825-4
Date
2017
Source
PLoS Biology   15: e2002257 (Journal)
Registered Authors
Dorsky, Richard, Gaynes, John, Panahi, Samin, Xie, Yuanyuan
Keywords
Zebrafish, Hypothalamus, Mice, Neurons, Embryos, In situ hybridization, RNA sequencing, Drosophila melanogaster
Datasets
GEO:GSE98519
MeSH Terms
  • Drosophila Proteins/genetics
  • Drosophila Proteins/metabolism
  • Humans
  • Animals
  • Genes, Reporter
  • Mutation
  • Behavior, Animal
  • Biomarkers/metabolism
  • Anxiety/metabolism
  • Anxiety/pathology
  • Anxiety/prevention & control*
  • Neurons/cytology
  • Neurons/metabolism*
  • Neurons/pathology
  • Species Specificity
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Mice, Knockout
  • Hypothalamus/cytology
  • Hypothalamus/metabolism*
  • Hypothalamus/pathology
  • Neurogenesis*
  • Mice, Transgenic
  • Male
  • Female
  • Drosophila melanogaster
  • Zebrafish
  • Gene Expression Regulation
  • Lymphoid Enhancer-Binding Factor 1/genetics
  • Lymphoid Enhancer-Binding Factor 1/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
(all 34)
PubMed
28837622 Full text @ PLoS Biol.
Abstract
While innate behaviors are conserved throughout the animal kingdom, it is unknown whether common signaling pathways regulate the development of neuronal populations mediating these behaviors in diverse organisms. Here, we demonstrate that the Wnt/ß-catenin effector Lef1 is required for the differentiation of anxiolytic hypothalamic neurons in zebrafish and mice, although the identity of Lef1-dependent genes and neurons differ between these 2 species. We further show that zebrafish and Drosophila have common Lef1-dependent gene expression in their respective neuroendocrine organs, consistent with a conserved pathway that has diverged in the mouse. Finally, orthologs of Lef1-dependent genes from both zebrafish and mouse show highly correlated hypothalamic expression in marmosets and humans, suggesting co-regulation of 2 parallel anxiolytic pathways in primates. These findings demonstrate that during evolution, a transcription factor can act through multiple mechanisms to generate a common behavioral output, and that Lef1 regulates circuit development that is fundamentally important for mediating anxiety in a wide variety of animal species.
Genes / Markers
Figures
Figure Gallery (6 images)
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
lef1zd11/zd11standard conditionsProtruding-mouth
lef1zd11/zd11standard conditionsProtruding-mouth
lef1zd11/zd11standard conditionsProtruding-mouth
lef1zd11/zd11standard conditionsProtruding-mouth
lef1zd11/zd11standard conditionsProtruding-mouth
lef1zd11/zd11standard conditionsProtruding-mouth
lef1zd11/zd11standard conditionsProtruding-mouth
lef1zd11/zd11standard conditionsProtruding-mouth
lef1zd11/zd11standard conditionsProtruding-mouth
lef1zd11/zd11standard conditionsProtruding-mouth
1 - 10 of 17
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
kca6TgTransgenic Insertion
    ot1TgTransgenic Insertion
      w25TgTransgenic Insertion
        zd11
          		Small Deletion
          zd201TgTransgenic Insertion
            zdf1
              		Point Mutation
              1 - 6 of 6
              Show
              Human Disease / Model
              Human Disease Fish Conditions Evidence
              anxiety disorderlef1zd11/zd11standard conditionsTAS
              1 - 1 of 1
              Show
              Sequence Targeting Reagents
              No data available
              Fish
              Fish
              lef1zd11/zd11
              lef1zd11/zd11; w25Tg
              w25Tg
              WT
              1 - 4 of 4
              Show
              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              AequorinEFGAequorin
              GFPEFGGFP
              1 - 2 of 2
              Show
              Mapping
              No data available
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              Citation
              Xie, Y., Kaufmann, D., Moulton, M.J., Panahi, S., Gaynes, J.A., Watters, H.N., Zhou, D., Xue, H.H., Fung, C.M., Levine, E.M., Letsou, A., Brennan, K.C., Dorsky, R.I. (2017) Lef1-dependent hypothalamic neurogenesis inhibits anxiety. PLoS Biology. 15:e2002257.