Lef1-dependent hypothalamic neurogenesis inhibits anxiety.

Xie Y, Kaufmann D, Moulton MJ, Panahi S, Gaynes JA, Watters HN, Zhou D, Xue HH, Fung CM, Levine EM, Letsou A, Brennan KC, Dorsky RI
PLoS Biol. 2017 15 (8): e2002257

PMID: 28837622 · PMCID: PMC5570277 · DOI:10.1371/journal.pbio.2002257

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.

MeSH Terms (23)

Animals Anxiety Behavior, Animal Biomarkers Drosophila melanogaster Drosophila Proteins Female Gene Expression Regulation Genes, Reporter Humans Hypothalamus Lymphoid Enhancer-Binding Factor 1 Male Mice, Knockout Mice, Transgenic Mutation Nerve Tissue Proteins Neurogenesis Neurons Species Specificity Transcription Factors Zebrafish Zebrafish Proteins

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