Evolutionarily conserved regulation of hypocretin neuron specification by Lhx9

Liu, Justin and Merkle, Florian T. and Gandhi, Avni V. and Gagnon, James A. and Woods, Ian G. and Chiu, Cindy N. and Shimogori, Tomomi and Schier, Alexander F. and Prober, David A.. (2015) Evolutionarily conserved regulation of hypocretin neuron specification by Lhx9. Development, 142 (6). pp. 1113-1124.

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Official URL: https://edoc.unibas.ch/74130/

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Loss of neurons that express the neuropeptide hypocretin (Hcrt) has been implicated in narcolepsy, a debilitating disorder characterized by excessive daytime sleepiness and cataplexy. Cell replacement therapy, using Hcrt-expressing neurons generated in vitro, is a potentially useful therapeutic approach, but factors sufficient to specify Hcrt neurons are unknown. Using zebrafish as a high-throughput system to screen for factors that can specify Hcrt neurons in vivo, we identified the LIM homeobox transcription factor Lhx9 as necessary and sufficient to specify Hcrt neurons. We found that Lhx9 can directly induce hcrt expression and we identified two potential Lhx9 binding sites in the zebrafish hcrt promoter. Akin to its function in zebrafish, we found that Lhx9 is sufficient to specify Hcrt-expressing neurons in the developing mouse hypothalamus. Our results elucidate an evolutionarily conserved role for Lhx9 in Hcrt neuron specification that improves our understanding of Hcrt neuron development.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell and Developmental Biology (Schier)
UniBasel Contributors:Schier, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Company of Biologists
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2020 19:33
Deposited On:24 May 2020 19:33

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