PUBLICATION

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States

Authors

Chiu, C.N., Rihel, J., Lee, D.A., Singh, C., Mosser, E.A., Chen, S., Sapin, V., Pham, U., Engle, J., Niles, B.J., Montz, C.J., Chakravarthy, S., Zimmerman, S., Salehi-Ashtiani, K., Vidal, M., Schier, A.F., Prober, D.A.

ID

ZDB-PUB-160219-7

Date

2016

Source

Neuron 89: 842-856 (Journal)

Registered Authors

Prober, David, Rihel, Jason, Schier, Alexander, Zimmerman, Steve

Keywords

none

MeSH Terms

Age Factors
Mice, Transgenic
Signal Transduction/drug effects
Signal Transduction/genetics
Zebrafish Proteins/genetics
Motor Activity/genetics
Humans
Receptors, Complement 3b/metabolism
Receptors, Neurotransmitter/metabolism
Aniline Compounds/pharmacology
Neuropeptides/genetics*
Neuropeptides/metabolism*
Brain Stem/cytology
Brain Stem/growth & development
Brain Stem/metabolism
Animals
Gene Expression Regulation/drug effects
Gene Expression Regulation/genetics*
Larva
Zebrafish
Pyrimidines/pharmacology
Sleep/genetics*
Pituitary-Adrenal System/metabolism
Hypothalamo-Hypophyseal System/metabolism
Neurons/drug effects
Neurons/metabolism
Wakefulness/genetics*

(all 27)

PubMed

26889812 Full text @ Neuron

Abstract

Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotropin releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather probably acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway. VIDEO ABSTRACT.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
crhb	ct830Tg	heat shock	Day 5	brainstem	ISH	Fig. 7
crhb	ct830Tg	heat shock	Day 5	diencephalon	ISH	Fig. 7
crhb	WT	heat shock	Day 5	brainstem	ISH	Fig. 7
crhb	WT	heat shock	Day 5	diencephalon	ISH	Fig. 7
fosab	ct830Tg	heat shock	Day 5	brain	ISH	Fig. 7
fosab	ct830Tg	heat shock	Day 5	brainstem	ISH	Fig. 7
fosab	ct830Tg	heat shock	Day 5	diencephalon	ISH	Fig. 7
fosab	WT	heat shock	Day 5	brain	ISH	Fig. 7
fosab	WT	heat shock	Day 5	brainstem	ISH	Fig. 7
fosab	WT	heat shock	Day 5	diencephalon	ISH	Fig. 7

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	heat shock, chemical treatment: 5-chloro-N4-(cyclopropylmethyl)-2-methyl-N4-propyl-N6-(2,4,6-trichlorophenyl)pyrimidine-4,6-diamine	Day 5	swimming behavior decreased occurrence, abnormal	Fig. 7
ct830Tg	heat shock	Day 5	brain fosab expression increased amount, abnormal	Fig. 7
ct830Tg	heat shock	Day 5	brain fosab expression increased distribution, abnormal	Fig. 7
ct830Tg	heat shock	Day 5	brain fosab expression spatial pattern, abnormal	Fig. 7
ct830Tg	heat shock	Day 5	swimming behavior increased occurrence, abnormal	Fig. 7
ct830Tg	heat shock, chemical treatment: 5-chloro-N4-(cyclopropylmethyl)-2-methyl-N4-propyl-N6-(2,4,6-trichlorophenyl)pyrimidine-4,6-diamine	Day 5	swimming behavior increased occurrence, ameliorated	Fig. 7
ct830Tg/+	heat shock	Day 6	circadian behavior disrupted, abnormal	text only
ct830Tg/+	heat shock	Day 6	response to light stimulus increased behavioural activity, abnormal	text only
ct830Tg/+	heat shock	Day 6	sleep decreased duration, abnormal	text only
ct830Tg/+	heat shock	Day 6	sleep decreased occurrence, abnormal	text only

1 - 10 of 56

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ct810		Small Deletion	nmu
ct827		Indel	nmur1a
ct828		Small Deletion	nmur1b
ct829		Small Deletion	nmur3
ct830Tg	Tg(hsp70l:nmu)	Transgenic Insertion
s357		Point Mutation	nr3c1

1 - 6 of 6

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
ct830Tg
ct830Tg/+
nmur1a^ct827/ct827
nmur1a^ct827/+
nmur1b^ct828/ct828
nmur1b^ct828/+
nmur3^ct829/ct829
nmur3^ct829/ct829; ct830Tg/+
nmur3^ct829/+
nmur3^ct829/+; ct830Tg

Antibodies

Orthology

Gene	Orthology
nmu
nmur1a
nmur1b

Engineered Foreign Genes

Mapping

Chiu et al., 2016 ZDB-PUB-160219-7 PMID:26889812

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States

Chiu et al., 2016

ZDB-PUB-160219-7
PMID:26889812