Morphometric Analysis of Huntington’s Disease Neurodegeneration in Drosophila

Song, Wan; Smith, Marianne R.; Syed, Adeela; Lukácsovich, Tamás; Barbaro, Brett A.; Purcell, Judith; Bornemann, Doug J.; Burke, John J.; Marsh, J. Lawrence

doi:10.1007/978-1-62703-438-8_3

Cited by 25 publications

(22 citation statements)

References 45 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Curcumin also ameliorates the extensive degeneration and external dysmorphology of the eye, caused by the expression of Httex1pQ93 in all of the cells of the Drosophila’s eye [110]. This progressive loss of photoreceptor cells expressing httex1pQ93 and Q48 peptides can be observed quantitatively (as a measure of neurodegeneration) with the pseudopupil technique [111]. Nurturing the fly httex1pQ93 and Q48 with curcumin-supplemented food was enough to suppress the photoreceptor neuron degeneration in a dose-dependent manner.…”

Section: The Legacy Of Fly Models In Hdmentioning

confidence: 99%

The Tiny Drosophila Melanogaster for the Biggest Answers in Huntington’s Disease

Rosas‐Arellano

Estrada-Mondragón

Piña

et al. 2018

IJMS

View full text Add to dashboard Cite

The average life expectancy for humans has increased over the last years. However, the quality of the later stages of life is low and is considered a public health issue of global importance. Late adulthood and the transition into the later stage of life occasionally leads to neurodegenerative diseases that selectively affect different types of neurons and brain regions, producing motor dysfunctions, cognitive impairment, and psychiatric disorders that are progressive, irreversible, without remission periods, and incurable. Huntington’s disease (HD) is a common neurodegenerative disorder. In the 25 years since the mutation of the huntingtin (HTT) gene was identified as the molecule responsible for this neural disorder, a variety of animal models, including the fruit fly, have been used to study the disease. Here, we review recent research that used Drosophila as an experimental tool for improving knowledge about the molecular and cellular mechanisms underpinning HD.

show abstract

Section: The Legacy Of Fly Models In Hdmentioning

confidence: 99%

The Tiny Drosophila Melanogaster for the Biggest Answers in Huntington’s Disease

Rosas‐Arellano

Estrada-Mondragón

Piña

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…This time contrasts to the several days needed to analyze retinal parameters from fixed tissues and pictures from SEM, TEM or standard histological sections [ 8 - 10 ]. Another advantage of our methodology is the number of ommatidia explored in each ROI of a single fly (over 200/sample), in comparison with the 30–40 ommatidia counted in each eye when using the deep pseudopupil technique [ 7 ].…”

Section: Resultsmentioning

confidence: 99%

An automated image analysis method to measure regularity in biological patterns: a case study in a Drosophila neurodegenerative model

Díez-Hermano

Valero

Rueda

et al. 2015

Mol Neurodegeneration

View full text Add to dashboard Cite

The fruitfly compound eye has been broadly used as a model for neurodegenerative diseases. Classical quantitative techniques to estimate the degeneration level of an eye under certain experimental conditions rely either on time consuming histological techniques to measure retinal thickness, or pseudopupil visualization and manual counting. Alternatively, visual examination of the eye surface appearance gives only a qualitative approximation provided the observer is well-trained. Therefore, there is a need for a simplified and standardized analysis of fruitfly eye degeneration extent for both routine laboratory use and for automated high-throughput analysis. We have designed the freely available ImageJ plugin FLEYE, a novel and user-friendly method for quantitative unbiased evaluation of neurodegeneration levels based on the acquisition of fly eye surface pictures. The incorporation of automated image analysis tools and a classification algorithm sustained on a built-in statistical model allow the user to quickly analyze large sample size data with reliability and robustness. Pharmacological screenings or genetic studies using the Drosophila retina as a model system may benefit from our method, because it can be easily implemented in a fully automated environment. In addition, FLEYE can be trained to optimize the image detection capabilities, resulting in a versatile approach to evaluate the pattern regularity of other biological or non-biological samples and their experimental or pathological disruption.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-015-0005-z) contains supplementary material, which is available to authorized users.

show abstract

“…We note that Flynotyper is not an alternative to visual inspection or other phenotypic methods of the eye. Rather, it is a tool that will complement other existing assays, such as the thin sectioning of the eye (46), pseudopupil analysis (47) and semiautomated methods to measure eye size (38)(39)(40), neurodegeneration (48,49), and pupal eye patterning (50), to enable more accurate measurement of genetic effects (Figure S14). The strengths of Flynotyper will enhance the sensitivity of studies that use rough eye phenotypes for understanding the effects and interactions of genes involved in various biological processes.…”

Section: Discussionmentioning

confidence: 99%

Quantitative assessment of eye phenotypes for functional genetic studies usingDrosophila melanogaster

Iyer

Wang

et al. 2016

Preprint

View full text Add to dashboard Cite

About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/ degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions.

show abstract

Morphometric Analysis of Huntington’s Disease Neurodegeneration in Drosophila

Cited by 25 publications

References 45 publications

The Tiny Drosophila Melanogaster for the Biggest Answers in Huntington’s Disease

The Tiny Drosophila Melanogaster for the Biggest Answers in Huntington’s Disease

An automated image analysis method to measure regularity in biological patterns: a case study in a Drosophila neurodegenerative model

Quantitative assessment of eye phenotypes for functional genetic studies usingDrosophila melanogaster

Contact Info

Product

Resources

About