Origins of Survival Behaviors

The hypothalamus is a critical regulator of many physiological processes and behaviors that are essential for life. Each anatomically-defined hypothalamic nucleus consists of functionally heterogeneous neuronal subpopulations that dictate distinct survival skills such as feeding, mating, and parental care.

We study how the developing hypothalamus generates diverse neuronal identities that ultimately give rise to distinct survival behaviors. We began with two intermingled neuronal subpopulations in the arcuate nucleus of the hypothalamus that play a critical role in the control of satiety. Neurons that produce the orexigenic neuropeptide Y (NPY) and agouti-related protein (AgRP) directly stimulate food intake, whereas those synthesizing the anorexigenic peptide pro-opiomelanocortin (POMC) suppress feeding. Despite their opposing actions on food intake in the adult brain, POMC and NPY/AgRP neurons are derived from the same neuronal progenitors during early differentiation. However, mechanisms through which common neuronal precursors subsequently adopt either the anorexigenic or the orexigenic identity—remain elusive. We speculate the POMC and the NPY/AgRP cell fates are specified and maintained by distinct transcriptional programs. To this end, we profiled the transcriptomes of genetically-labeled POMC and NPY/AgRP neurons in the developing hypothalamus using whole-genome RNA sequencing. Through cell type-specific transcriptomics analysis, we identified several transcription regulators that are uniquely enriched in one of the two populations.

We are currently investigating the roles of these factors in specifying and maintaining cellular and functional identities in the hypothalamus.