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

• Published in: Communications biology Vol. 4; no. 1; p. 95
• Main Authors: Kim, Dong Won, Liu, Kai, Wang, Zoe Qianyi, Zhang, Yi Stephanie, Bathini, Abhijith, Brown, Matthew P., Lin, Sonia Hao, Washington, Parris Whitney, Sun, Changyu, Lindtner, Susan, Lee, Bora, Wang, Hong, Shimogori, Tomomi, Rubenstein, John L. R., Blackshaw, Seth
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21-01-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1385/519; 631/378/2571/1696; 631/378/2571/2578; Animals; Biology; Biomedical and Life Sciences; Cell Differentiation; Cell Survival; GABAergic Neurons - physiology; Gene Regulatory Networks; Homeobox; Homeobox Protein Nkx-2.2; Homeodomain Proteins - metabolism; Hypothalamus; Hypothalamus - cytology; Hypothalamus - metabolism; Interneurons; Life Sciences; LIM-Homeodomain Proteins - metabolism; Mice; Molecular modelling; Nerve Tissue Proteins - metabolism; Neuropeptides; Nkx2.2 protein; Nuclear Proteins; Sleep; Sleep - physiology; Telencephalon; Thyroid transcription factor 1; Transcription Factors - metabolism; Zona incerta; γ-Aminobutyric acid
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-01616-7

GABAergic neurons of the hypothalamus regulate many innate behaviors, but little is known about the mechanisms that control their development. We previously identified hypothalamic neurons that express the LIM homeodomain transcription factor Lhx6, 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 the survival of hypothalamic neurons.
Dlx1/2
,
Nkx2-2
, and
Nkx2-1
are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons, and that Nkx2-2+/Lhx6+ neurons of the zona incerta are responsive to sleep pressure. We further identify multiple neuropeptides that are enriched in spatially segregated subsets of hypothalamic Lhx6 neurons, and that are distinct from those seen in cortical neurons. These findings identify common and divergent molecular mechanisms by which Lhx6 controls the development of GABAergic neurons in the hypothalamus.
Dong Won Kim and colleagues investigate the mechanisms by which hypothalamic GABAergic neurons differentiate during development. They report that
Lhx6
is crucial for the survival of hypothalamic neurons.