Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons.

GABAergic neurons of the hypothalamus regulate many innate behaviours, but little is known about the mechanisms controlling their development. We previously identified hypothalamic neurons expressing the LIM homeodomain transcription factor Lhx6, also a master regulator of cortical interneuron development, as sleep-promoting. In contrast to telencephalic interneurons, hypothalamic Lhx6 neurons do not undergo long-distance tangential migration, and do not express cortical interneuronal markers such as Pvalb. Here, we show that Lhx6 is necessary for survival of hypothalamic neurons, and that Dlx1/2, Nkx2-2, and Nkx2-1 are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons. We identify a broad range of neuropeptides that are enriched in spatially segregated subsets of hypothalamic Lhx6 neurons, and distinct from those seen in cortical neurons. These findings identify common and divergent mechanisms by which Lhx6 controls the development of GABAergic neurons in the hypothalamus compared to telencephalic interneurons.