ZFIN ID: ZDB-PUB-170825-4
Lef1-dependent hypothalamic neurogenesis inhibits anxiety
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.
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
Microarrays: GEO:GSE98519
MeSH Terms:
  • Animals
  • Anxiety/metabolism
  • Anxiety/pathology
  • Anxiety/prevention & control*
  • Behavior, Animal
  • Biomarkers/metabolism
  • Drosophila Proteins/genetics
  • Drosophila Proteins/metabolism
  • Drosophila melanogaster
  • Female
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Hypothalamus/cytology
  • Hypothalamus/metabolism*
  • Hypothalamus/pathology
  • Lymphoid Enhancer-Binding Factor 1/genetics
  • Lymphoid Enhancer-Binding Factor 1/metabolism*
  • Male
  • Mice, Knockout
  • Mice, Transgenic
  • Mutation
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Neurogenesis*
  • Neurons/cytology
  • Neurons/metabolism*
  • Neurons/pathology
  • Species Specificity
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28837622 Full text @ PLoS Biol.
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.