Dopamine transporter expression distinguishes dopaminergic neurons from other catecholaminergic neurons in the developing zebrafish embryo

Holzschuh, Jochen; Ryu, Soojin; Aberger, Fritz; Driever, Wolfgang

doi:10.1016/s0925-4773(01)00287-8

Cited by 246 publications

(264 citation statements)

References 18 publications

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“…1 E and F). To test whether the differentiation of cells from other retinal layers is affected, we used th expression to mark the dopaminergic subset of amacrine cells within the inner nuclear layer (17) and rhodopsin expression to label photoreceptors. We detected both of these neuronal types in mutant retinae, although their cell number was severely reduced (Fig.…”

Section: Results M850 Mutant Embryos Display Reduction In Cell Numbermentioning

confidence: 99%

Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis

Ryu

Holzschuh

Erhardt

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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In multicellular organisms, the control of genome duplication and cell division must be tightly coordinated. Essential roles of the minichromosome maintenance (MCM) proteins for genome duplication have been well established. However, no genetic model has been available to address the function of MCM proteins in the context of vertebrate organogenesis. Here, we present positional cloning of a zebrafish mcm5 mutation and characterization of its retina phenotype. In the retina, mcm5 expression correlates closely with the pattern of cell proliferation. By the third day of development, mcm5 is down-regulated in differentiated cells but is maintained in regions containing retinal stem cells. We demonstrate that a gradual depletion of maternally derived MCM5 protein leads to a prolonged S phase, cell-cycle-exit failure, apoptosis, and reduction in cell number in mcm5 m850 mutant embryos. Interestingly, by the third day of development, increased apoptosis is detectable only in the retina, tectum, and hindbrain but not in other late-proliferating tissues, suggesting that different tissues may employ distinct cellular programs in responding to the depletion of MCM5.stem cell ͉ cell proliferation ͉ ciliary marginal zone ͉ embryogenesis ͉ development P roper duplication of the genome during the cell cycle is of paramount importance for the life of an organism. In eukaryotes, each replication origin is ''licensed'' to fire once per cell cycle through the cell-cycle-dependent formation and destruction of a prereplication complex (preRC) (1-3). A key component of this preRC is a family of six structurally related proteins, MCM2 through -7, which are evolutionarily conserved in all eukaryotes. The MCM proteins were originally identified as proteins required for minichromosome maintenance in Saccharomyces cerevisiae (4). MCM2 through -7 belong to a distinct subgroup of the large AAAϩ ATPase family (5) and share a conserved central region of Ϸ200 amino acids (MCM box). Biochemical studies in Xenopus have established the role of MCM2 through -7 as replication-licensing factors (6-8). Subsequent studies illustrate that proper orchestration of the functional interactions among MCM2 through -7 proteins and other components of the preRC by cell-cycledependent protein kinases results in initiation of DNA synthesis once every cell cycle (9, 10). The MCM2 through -7 proteins appear to form heterohexamers and play important roles in initiation and elongation during DNA replication (4,11,12). Furthermore, recent evidence supports involvement of MCMs in many other chromosome transactions, including transcription, chromatin remodeling, and genome stability (13). However, in vivo analysis of MCMprotein functions in multicellular organism has been scarce. Here, we report the isolation, positional cloning, and in-depth characterization of a vertebrate mutant in an MCM-family protein. We demonstrate that the zebrafish m850 allele harbors a mutation in the mcm5 gene and exhibits developmental defects in lateproliferating tissues, including the re...

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Section: Results M850 Mutant Embryos Display Reduction In Cell Numbermentioning

confidence: 99%

Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis

Ryu

Holzschuh

Erhardt

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…The distribution and development of dopaminergic neurons during zebrafish embryogenesis has been studied recently (Guo et al, 1999;Holzschuh et al, 2001;Rink and Wullimann, 2002b). In mammals, dopaminergic neurons develop in the forebrain and midbrain.…”

Section: Discussionmentioning

confidence: 99%

“…Several reports have now described the organization and function of the dopamine system in zebrafish. Clusters of dopaminergic neurons have been identified in the developing embryo (Guo et al, 1999;Holzschuh et al, 2001;Rink and Wullimann, 2002b) and adult (Ma, 1994a(Ma, , b, 1997(Ma, , 2003. Immunocytochemical evidence suggests that zebrafish have a conserved dopaminergic projection pathway that is homologous to the human mesostriatal pathway (Rink and Wullimann, 2002a).…”

Section: Introductionmentioning

confidence: 99%

Evolution and expression of D2 and D3 dopamine receptor genes in zebrafish

Boehmler

Obrecht-Pflumio

Canfield

et al. 2004

Developmental Dynamics

143

122

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We mined the zebrafish genomic sequence database and identified contigs containing segments of several dopamine receptor genes. By using a polymerase chain reaction amplification strategy, we generated full-length cDNAs encoding a single dopamine D3 receptor and three distinct D2 receptor subtypes. Zebrafish dopamine receptor genes were mapped by using the T51 radiation hybrid panel. The D3 receptor gene (drd3) mapped to linkage group (LG) 24. The three D2 receptor genes were localized to LG 15 (drd2a), LG 16, (drd2b), and LG 5 (drd2c). With the exception of the drd2b gene, each of these map positions was syntenic with regions of human chromosomes containing orthologs of the zebrafish dopamine receptor genes. Whole-mount in situ hybridization was used to investigate expression of the D2 and D3 receptor genes. Expression of the drd3 gene was first detected at mid-somitogenesis and was particularly prominent in somites. Thereafter, the drd3 gene was expressed diffusely throughout the brain and spinal cord. The three D2 receptor genes were expressed throughout the central nervous system (CNS) in distinct but overlapping patterns. In early embryos, the drd2a gene was expressed exclusively in the epiphysis, whereas the drd2c gene was localized to the notochord. After 24 hpf, the drd2a, drd2b, and drd2c genes were differentially expressed throughout the CNS. The identification of dopamine receptor genes in zebrafish should allow us to use the power of zebrafish genetics to analyze the functional properties of this important class of neurotransmitter receptors.

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“…5 A and B correspond to aminergic neurons in the olfactory bulb and telencephalon of ETvmat2:GFP zebrafish (26) embryos; the posterior clusters contain the diencephalon. These clusters are predominantly dopaminergic, although they also include some (nor)adrenergic neurons (27). Exposure to 1 μM benomyl from 5 h until 120 h postfertilization resulted in a 24 ± 9% decrease in VMAT2 + (vesicular monoamine transporter) neuronal counts in anterior clusters (P = 0.041, n = 19; Fig.…”

Section: Aldh Inhibition In Primary Neurons and Mitochondrial Preparamentioning

confidence: 93%

Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease

Fitzmaurice

Rhodes²,

Lulla³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

177

139

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Parkinson disease (PD) is a neurodegenerative disorder particularly characterized by the loss of dopaminergic neurons in the substantia nigra. Pesticide exposure has been associated with PD occurrence, and we previously reported that the fungicide benomyl interferes with several cellular processes potentially relevant to PD pathogenesis. Here we propose that benomyl, via its bioactivated thiocarbamate sulfoxide metabolite, inhibits aldehyde dehydrogenase (ALDH), leading to accumulation of the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), preferential degeneration of dopaminergic neurons, and development of PD. This hypothesis is supported by multiple lines of evidence. (i) We previously showed in mice the metabolism of benomyl to S-methyl N-butylthiocarbamate sulfoxide, which inhibits ALDH at nanomolar levels. We report here that benomyl exposure in primary mesencephalic neurons (ii) inhibits ALDH and (iii) alters dopamine homeostasis. It induces selective dopaminergic neuronal damage (iv) in vitro in primary mesencephalic cultures and (v) in vivo in a zebrafish system. (vi) In vitro cell loss was attenuated by reducing DOPAL formation. (vii) In our epidemiology study, higher exposure to benomyl was associated with increased PD risk. This ALDH model for PD etiology may help explain the selective vulnerability of dopaminergic neurons in PD and provide a potential mechanism through which environmental toxicants contribute to PD pathogenesis.

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Dopamine transporter expression distinguishes dopaminergic neurons from other catecholaminergic neurons in the developing zebrafish embryo

Cited by 246 publications

References 18 publications

Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis

Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis

Evolution and expression of D2 and D3 dopamine receptor genes in zebrafish

Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease

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