TY - JOUR
T1 - Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons
AU - Kim, Dong Won
AU - Liu, Kai
AU - Wang, Zoe Qianyi
AU - Zhang, Yi Stephanie
AU - Bathini, Abhijith
AU - Brown, Matthew P.
AU - Lin, Sonia Hao
AU - Washington, Parris Whitney
AU - Sun, Changyu
AU - Lindtner, Susan
AU - Lee, Bora
AU - Wang, Hong
AU - Shimogori, Tomomi
AU - Rubenstein, John L.R.
AU - Blackshaw, Seth
N1 - Funding Information:
This work was supported by a grant from the NIH (R01DK108230) to S.B., the Maryland Stem Cell Research Fund (2019-MSCRFF-5124) to D.W.K., and the Japan Society for the Promotion of Science to T.S. We thank Transcriptomics and Deep Sequencing Core (Johns Hopkins) for sequencing of bulk RNA-Seq, bulk ATAC-Seq and scRNA-Seq libraries, and Ross Flow Cytometry Core (Johns Hopkins) for flow sorting of Lhx6-GFP cells, and Microscope facility (Johns Hopkins MICFAC, supported by the award number S10OD018118). We thank Marysia Placzek and Wendy Yap for comments on the paper.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s42003-020-01616-7
DO - 10.1038/s42003-020-01616-7
M3 - Article
C2 - 33479483
AN - SCOPUS:85099861406
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 95
ER -