Evolutionarily Conserved Regulation of Hypocretin Neuron Specification by Lhx9

Overview

Journal Development

Specialty Biology

Date 2015 Mar 1

PMID 25725064

Citations 43

Authors

Justin Liu

Florian T Merkle

Avni V Gandhi

James A Gagnon

Ian G Woods

Cindy N Chiu

Tomomi Shimogori

Alexander F Schier

David A Prober

Affiliations

Soon will be listed here.

Abstract

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.

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