Specification of Select Hypothalamic Circuits and Innate Behaviors by the Embryonic Patterning Gene Dbx1

Abstract

SUMMARY The hypothalamus integrates information required for the production of a variety of innate behaviors such as feeding, mating, aggression and predator avoidance. Despite an extensive knowledge of hypothalamic function, how embryonic genetic programs specify circuits that regulate these behaviors remains unknown. Here, we find that in the hypothalamus the developmentally regulated homeodomain-containing transcription factor Dbx1 is required for the generation of specific subclasses of neurons within the lateral hypothalamic area/zona incerta (LH) and the arcuate (Arc) nucleus. Consistent with this specific developmental role, Dbx1 hypothalamic-specific conditional-knockout mice display attenuated responses to predator odor and feeding stressors but do not display deficits in other innate behaviors such as mating or conspecific aggression. Thus, activity of a single developmentally regulated gene, Dbx1, is a shared requirement for the specification of hypothalamic nuclei governing a subset of innate behaviors.

Embryonic transcription factor expression in mice predicts medial amygdala neuronal identity and sex-specific responses to innate behavioral cues

“…To accomplish this, we exposed mice to rat odor, a well-characterized predator cue that evokes a strong aversive response in mice (Apfelbach et al, 2005; Carvalho et al, 2015; Sokolowski et al, 2015). Mice were exposed to soiled bedding from a rat cage (predator) or clean bedding (benign) as a control (Figure 7).…”

Development of the hypothalamus: conservation, modification and innovation

“…For example, Dbx1-dependent Agrp + /Npy + neurons in the ARC and Pmch + neurons in the lateral hypothalamic area (LHA) play a specific role in innate stress responses rather than their well-known function in feeding (Sokolowski et al, 2015). Similarly, Nkx2-1-dependent estrogen receptor alpha (ERα) + neurons in the VMH promote female locomotion instead of reproduction (Correa et al, 2015).…”

The cellular and molecular landscape of hypothalamic patterning and differentiation

“…These datasets have been used as the basis for genetic studies that selectively disrupt development of specific hypothalamic regions and/or cell types (20)(21)(22)(23)(24), leading in some cases to identification of novel functions for previously characterized hypothalamic regions or cell types (25,26). However, these datasets have important limitations: they do not provide cellular resolution of gene expression data, and they do not efficiently measure coexpression of multiple genes.…”