The genetic and molecular mechanisms that establish innate behaviors across diverse species are largely unknown. We have discovered an evolutionarily conserved role for Lef1-mediated Wnt signaling in the regulation of anxiety and in the differentiation of anxiolytic neurons in the zebrafish posterior hypothalamus. However mechanistic links between Lef1 targets, neurogenesis, and neuronal function in behavior have not yet been established. We also know that new neurons are continually added to this brain region, but it is not clear whether they contribute to anxiety-related behavior. This proposal will test the hypothesis that Lef1-mediated target genes regulate hypothalamic neurogenesis to control anxiety-related behavior throughout life.
Three specific aims will determine which Lef1 targets are required for the formation of anxiolytic neurons, whether those neurons regulate stress hormone levels through the HPI axis, and whether postembryonic Lef1-dependent neurogenesis can mediate behavior. Together this work will define a novel mechanism for the regulation of an innate behavior through neurogenesis.
Specific neuronal populations control evolutionarily conserved innate behaviors essential for survival, but the processes that generate these neurons are poorly understood. This work will define a novel role of the Wnt pathway mediator Lef1 in the continuous formation of hypothalamic neurons that regulate anxiety.
|Duncan, Robert N; Xie, Yuanyuan; McPherson, Adam D et al. (2016) Hypothalamic radial glia function as self-renewing neural progenitors in the absence of Wnt/?-catenin signaling. Development 143:45-53|
|McPherson, Adam D; Barrios, Joshua P; Luks-Morgan, Sasha J et al. (2016) Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers after Cell Ablation. Curr Biol 26:263-269|
|Duncan, Robert N; Panahi, Samin; Piotrowski, Tatjana et al. (2015) Identification of Wnt Genes Expressed in Neural Progenitor Zones during Zebrafish Brain Development. PLoS One 10:e0145810|