Tissue‐specific developmental requirements of <i>Drosophila</i> tyrosine hydroxylase isoforms

Friggi-Grelin, Florence; Iché, Magali; Birman, Serge

doi:10.1002/gene.10178

Cited by 38 publications

(18 citation statements)

References 46 publications

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“…More- over, we observed the restoration effect of L-DOPA on the impaired locomotion of parkin mutants and their significantly reduced dopamine level in the brain, which indirectly supports our result of the reduced TH staining level. Our hypothesis of a role of dopamine in locomotion in Drosophila could be further supported by previous studies demonstrating that the flies with reduced synaptic dopamine caused by overexpression of tetanus toxin under TH-GAL4 driver showed climbing impairment (42), and that L-DOPA and SK & F 38393 (prototypical D 1 receptor agonist) rescued the defective climbing ability induced by ␣-synuclein overexpression driven by the elav-GAL4 driver (43).…”

Section: Discussionsupporting

confidence: 58%

Parkin negatively regulates JNK pathway in the dopaminergic neurons ofDrosophila

Cha

Kim

Park

et al. 2005

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

232

192

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Parkin, an E3 ubiquitin ligase, has been found to be responsible for autosomal recessive juvenile parkinsonism characterized primarily by selective loss of dopaminergic neurons with subsequent defects in movements. However, the molecular mechanisms underlying this neuron loss remain elusive. Here, we characterized Drosophila parkin loss-of-function mutants, which exhibit shrinkage of dopaminergic neurons with decreased tyrosine hydroxylase level and impaired locomotion. The behavioral defect of parkin mutant flies was partially restored by administering L-DOPA, and the dopamine level in the brains of parkin mutant flies was highly decreased. Intriguingly, we found that c-Jun N-terminal kinase (JNK) is strongly activated in the dopaminergic neurons of parkin mutants and that impaired dopaminergic neuron phenotypes are dependent on the activation of the JNK signaling pathway. In consistent with this, our epistatic analysis and mammalian cell studies showed that Parkin inhibits the JNK signaling pathway in an E3 activity-dependent manner. These results suggest that loss of Parkin function up-regulates the JNK signaling pathway, which may contribute to the vulnerability of dopaminergic neurons in Drosophila parkin mutants and perhaps autosomal recessive juvenile parkinsonism patients.Parkinson's disease ͉ ubiquitination ͉ tyrosine hydroxylase ͉ degeneration ͉ apoptosis P arkinson's disease (PD) is the second most common neurodegenerative disease in North America, affecting Ͼ1 million people. The major symptoms of PD include rigidity, tremor, bradykinesia of the limbs, and postural instability. These symptoms result primarily from a deficiency of dopamine caused by selective degeneration of dopaminergic neurons in two regions of the brain, the substantia nigra pars compacta and striatum. Another pathological feature of this disease is the presence of inclusion bodies, called Lewy bodies, in those surviving neurons (1). The average onset of the disease is at the age of 60, but the pervasion of PD is not restricted to aging individuals; the onset of autosomal recessive juvenile parkinsonism (AR-JP) is usually between the age of 20 and 40 (2).Even though PD is largely a sporadic disorder, mutations in the genes responsible for PD, either autosomal dominant or recessive, have been found in a number of affected families. To date, six genes, namely, ␣-synuclein (PARK1) (3), parkin (PARK2) (4), UCH-L1 (PARK5) (5), PINK1 (PARK6) (6), DJ-1 (PARK7) (7), and the most recently identified, LRRK2͞dardarin (PARK8) (8, 9), have been isolated as pathological candidates for PD by family-based linkage analyses and positional cloning. Among them, mutations in parkin, PINK1, and DJ-1 were found to be associated with earlyonset autosomal recessive parkinsonism (4, 6, 7).In particular, Parkin is an E3 ubiquitin ligase, encoded by parkin, the most common gene mutated in familial PD. Although its exact in vivo function is not clearly revealed, the structure of Parkin gives significant clues to its possible function in the ubiquitination path...

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Section: Discussionsupporting

confidence: 58%

Parkin negatively regulates JNK pathway in the dopaminergic neurons ofDrosophila

Cha

Kim

Park

et al. 2005

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

232

192

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“…For example, alternative isoforms of the lola transcription factor have different functional domains, and mutations affecting the different isoforms have distinct phenotypes [57]. Similarly, one of the alternatively spliced transcripts of the Drosophila tyrosine hydroxylase ( pale ) is required for cuticle development, while a different transcript functions primarily in neurotransmission [62]. One dramatic example of alternative splicing is the cell adhesion receptor Dscam , which may produce up to 38,016 splicing variants [63,64].…”

Section: Discussionmentioning

confidence: 99%

Sex-specific expression of alternative transcripts in Drosophila

et al. 2006

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This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Sex-specific expression of alternative transcripts in Drosophila

A genome-wide microarray analysis of sex-specific expression of alternative transcripts in Drosophila shows sexual dimorphism in transcript abundance for 53% of the genes.

Abstract Background: Many genes produce multiple transcripts due to alternative splicing or utilization of alternative transcription initiation/termination sites. This 'transcriptome expansion' is thought to increase phenotypic complexity by allowing a single locus to produce several functionally distinct proteins. However, sex, genetic and developmental variation in the representation of alternative transcripts has never been examined systematically. Here, we describe a genome-wide analysis of sex-specific expression of alternative transcripts in Drosophila melanogaster.

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“…There are two main isoforms of ple; dopaminergic cells preferentially express the central nervous system-specific isoform that lacks exons 3 and 4 and not the hypodermal form ( Fig. 3; Friggi-Grelin, Iche, & Birman, 2003). In addition, only the circadian M-cells express substantial levels of timeless.…”

Section: Amplification Of Mrnamentioning

confidence: 98%