Abstract
The vertebrate hypothalamus regulates physiological and behavioral responses to environmental stimuli through the function of evolutionarily-conserved neuronal subpopulations. Our previous work found that mutation of zebrafish lef1 , which encodes a transcriptional mediator of the Wnt signaling pathway, leads to the loss of hypothalamic neurons and behavioral phenotypes that are both associated with stress-related human mood disorders However, the specific Lef1 target genes that link neurogenesis to behavior remain unknown. One candidate is otpb , which encodes a transcription factor with known roles in hypothalamic development. Here we show that otpb expression in the posterior hypothalamus is Lef1-dependent, and that like lef1 , its function is required for the generation of crhbp + neurons in this region. Transgenic reporter analysis of a crhbp conserved noncoding element suggests that otpb participates in a transcriptional regulatory network with other Lef1 targets. Finally, consistent with a role for crhbp in inhibiting the stress response, zebrafish otpb mutants exhibit decreased exploration in a novel tank diving assay. Together our findings suggest a potential evolutionarily-conserved mechanism for the regulation of innate stress response behaviors through Lef1-mediated hypothalamic neurogenesis.