Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern

Amanda R Decker; Matthew S McNeill; Aaron M Lambert; Jeffrey D Overton; Yu-Chia Chen; Ramón A Lorca; Nicolas A Johnson; Susan E Brockerhoff; Durga P Mohapatra; Heather MacArthur; Pertti Panula; Mark A Masino; Loren W Runnels; Robert A Cornell

doi:10.1016/j.ydbio.2013.11.015

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Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern

Journal article

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Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern

Amanda R Decker, Matthew S McNeill, Aaron M Lambert, Jeffrey D Overton, Yu-Chia Chen, Ramón A Lorca, Nicolas A Johnson, Susan E Brockerhoff, Durga P Mohapatra, Heather MacArthur, …

Developmental biology, Vol.386(2), pp.428-439

02/15/2014

DOI: 10.1016/j.ydbio.2013.11.015

PMCID: PMC3971878

PMID: 24291744

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Abstract

Transient receptor potential, melastatin-like 7 (Trpm7) is a combined ion channel and kinase implicated in the differentiation or function of many cell types. Early lethality in mice and frogs depleted of the corresponding gene impedes investigation of the functions of this protein particularly during later stages of development. By contrast, zebrafish trpm7 mutant larvae undergo early morphogenesis normally and thus do not have this limitation. The mutant larvae are characterized by multiple defects including melanocyte cell death, transient paralysis, and an ion imbalance that leads to the development of kidney stones. Here we report a requirement for Trpm7 in differentiation or function of dopaminergic neurons in vivo. First, trpm7 mutant larvae are hypomotile and fail to make a dopamine-dependent developmental transition in swim-bout length. Both of these deficits are partially rescued by the application of levodopa or dopamine. Second, histological analysis reveals that in trpm7 mutants a significant fraction of dopaminergic neurons lack expression of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Third, trpm7 mutants are unusually sensitive to the neurotoxin 1-methyl-4-phenylpyridinium, an oxidative stressor, and their motility is partially rescued by application of the iron chelator deferoxamine, an anti-oxidant. Finally, in SH-SY5Y cells, which model aspects of human dopaminergic neurons, forced expression of a channel-dead variant of TRPM7 causes cell death. In summary, a forward genetic screen in zebrafish has revealed that both melanocytes and dopaminergic neurons depend on the ion channel Trpm7. The mechanistic underpinning of this dependence requires further investigation. •Zebrafish trpm7 mutant larvae exhibit dopamine-responsive behavioral deficits.•In such larvae, dopaminergic neurons express DAT but many lack expression of TH.•trpm7 mutant larvae are hyper-sensitive to a toxin of dopaminergic neurons, MPP+.•We show that SH-SY5Y cells, which are dopaminergic, depend on TRPM7 for survival.•How Trpm7 contributes to function and viability of dopaminergic neurons is unknown.

Parkinson's

Zebrafish

TRPM7

Dopamine

Details

Title: Subtitle: Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern
Creators: Amanda R Decker - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, United States
Matthew S McNeill - Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA 52242, United States
Aaron M Lambert - Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, United States
Jeffrey D Overton - UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States
Yu-Chia Chen - Neuroscience Center and Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland
Ramón A Lorca - Department of Pharmacology, University of Iowa, Iowa City, IA 52245, United States
Nicolas A Johnson - Department of Biochemistry, University of Washington, Seattle, WA 98195, United States
Susan E Brockerhoff - Department of Biochemistry, University of Washington, Seattle, WA 98195, United States
Durga P Mohapatra - Department of Pharmacology, University of Iowa, Iowa City, IA 52245, United States
Heather MacArthur - Department of Pharmacological and Physiological Science, St. Louis University, St. Louis, MO 63104, United States
Pertti Panula - Neuroscience Center and Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland
Mark A Masino - Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, United States
Loren W Runnels - UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States
Robert A Cornell - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, United States
Resource Type: Journal article
Publication Details: Developmental biology, Vol.386(2), pp.428-439
DOI: 10.1016/j.ydbio.2013.11.015
PMID: 24291744
PMCID: PMC3971878
NLM abbreviation: Dev Biol
ISSN: 0012-1606
eISSN: 1095-564X
Publisher: Elsevier Inc
Grant note: name: University of Iowa Environmental Health Sciences Research Center, award: GM067841, R01EY018814, R01EY015165, P30EY001730, NS069898, NS065054, RO1GM080753; DOI: 10.13039/501100002341, name: Academy of Finland, award: 116177; name: Sigrid Juselius Foundation
Language: English
Date published: 02/15/2014
Academic Unit: Psychiatry; Anatomy and Cell Biology; Dental Research
Record Identifier: 9984025314102771

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