Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias

Stubenhaus, Bradford M; Dustin, John P.; Neverett, Emily R; Beaudry, Megan S; Nadeau, Leanna E; Burk-McCoy, Ethan; He, Xinwen; Pearson, Bret J.; Pellettieri, Jason

doi:10.7554/elife.14175

Cited by 31 publications

(42 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Enzymes of the tryptophan catabolism pathway have been known for several decades, mainly from the availability of two D. melanogaster mutants: vermilion and cinnabar (Linzen, ; Summers et al, ). These enzymes and their genes have since been characterised in many different insects (Table ), and also in planarians (Stubenhaus et al, ; He et al, ), implying their conservation in protostomes (Fig. ).…”

Section: Ommochrome Biochemistry: From the Indole To The Phenoxazone mentioning

confidence: 99%

See 1 more Smart Citation

Ommochromes in invertebrates: biochemistry and cell biology

2018

View full text Add to dashboard Cite

Ommochromes are widely occurring coloured molecules of invertebrates, arising from tryptophan catabolism through the so-called Tryptophan → Ommochrome pathway. They are mainly known to mediate compound eye vision, as well as reversible and irreversible colour patterning. Ommochromes might also be involved in cell homeostasis by detoxifying free tryptophan and buffering oxidative stress. These biological functions are directly linked to their unique chromophore, the phenoxazine/phenothiazine system. The most recent reviews on ommochrome biochemistry were published more than 30 years ago, since when new results on the enzymes of the ommochrome pathway, on ommochrome photochemistry as well as on their antiradical capacities have been obtained. Ommochromasomes are the organelles where ommochromes are synthesised and stored. Hence, they play an important role in mediating ommochrome functions. Ommochromasomes are part of the lysosome-related organelles (LROs) family, which includes other pigmented organelles such as vertebrate melanosomes. Ommochromasomes are unique because they are the only LRO for which a recycling process during reversible colour change has been described. Herein, we provide an update on ommochrome biochemistry, photoreactivity and antiradical capacities to explain their diversity and behaviour both in vivo and in vitro. We also highlight new biochemical techniques, such as quantum chemistry, metabolomics and crystallography, which could lead to major advances in their chemical and functional characterisation. We then focus on ommochromasome structure and formation by drawing parallels with the well-characterised melanosomes of vertebrates. The biochemical, genetic, cellular and microscopic tools that have been applied to melanosomes should provide important information on the ommochromasome life cycle. We propose LRO-based models for ommochromasome biogenesis and recycling that could be tested in the future. Using the context of insect compound eyes, we finally emphasise the importance of an integrated approach in understanding the biological functions of ommochromes.

show abstract

Section: Ommochrome Biochemistry: From the Indole To The Phenoxazone mentioning

confidence: 99%

“…Photograph credits (all CC BY SA): (A) Sanjay Acharya, (B) Ash Bowie, (C) Magne Flåten, (D) Alpsdake, (E) Fritz Geller‐Grimm, Paul‐Henri Cahier and Hectonichus, (F) adapted from Hans Hillewaert, (G) adapted from Stubenhaus et al . () https://doi.org/10.7554/eLife.14175.003.…”

Section: Introductionmentioning

confidence: 99%

Ommochromes in invertebrates: biochemistry and cell biology

2018

View full text Add to dashboard Cite

show abstract

“…Coloration of those pigments resembled eye pigment cup cells. While three types of pigments – porphyrine, ommochrome, and melanin have been identified in planarians, melanin-based pigments are only produced by the pigmented optic cup cells of the planarian eye [21], [22]. These melanin pigments are the least sensitive to light exposure and remain detectable after standard bleaching procedures of exposure to light and hydrogen peroxide (Additional file: Fig.…”

Section: Resultsmentioning

confidence: 99%

S-adenosylhomocysteine hydrolase regulates anterior patterning inDugesia japonica

Reinmets

Bischof

Taketa

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundBiological methylation requires S-adenosylmethionine (SAM) and participates in a range of processes from modulation of gene expression via histone modifications to neurotransmitter synthesis. An important factor in all methylation reactions is the concentration ratio of SAM to methylation byproduct S-adenosylhomocysteine (SAH). SAH hydrolase, also known as adenosylhomocysteinase, depletes SAH and thereby facilitates metabolite recycling and maintains the methylation permissive SAM/SAH ratio. While the importance of SAH hydrolase in sustaining methylation is obvious on the cellular level, the function of this metabolic process on the organismal scale is not clear.ResultsWe used planarian Dugesia japonica to investigate the role SAH hydrolase in physiological homeostasis on the body-wide scale. Remarkably, pharmacological inhibition of the SAH hydrolase results in regression of anterior tissues and is accompanied by extensive apoptosis throughout the planarian body. Moreover, exposure to the SAHH inhibitor AdOx leads to changes in brain morphology and spatial shift in the expression of Wnt-modulator Notum. Strikingly, planarians are able to overcome these destructive patterning defects through regeneration of the anterior tissues and adaptation to the used inhibitor. Transcriptome analysis indicates that resistance to the SAHH inhibitor is at least partly mediated by changes in folate cycle and lipid metabolism.ConclusionsSAH hydrolase plays a critical role in planarian homeostasis and anterior patterning potentially through modulation of Wnt signaling. Moreover, planarian adaptation to the SAHH inhibitor via metabolic reprogramming suggests potential targets for addressing methylation-related human conditions.

show abstract

“…This exciting prospect that a hox gene does affect planarian tissues represents a potential future project. An example of a follow‐up project initiated by undergraduates was the discovery of light‐induced depigmentation in planarians that helped establish these animals as an experimentally tractable model for research into the pathophysiology of acute porphyrias .…”

Section: Resultsmentioning

confidence: 99%

A modular laboratory course using planarians to study genes involved in tissue regeneration

Ochoa

Dores

Allen

et al. 2019

Biochem Molecular Bio Educ

View full text Add to dashboard Cite

Undergraduate research experiences are excellent opportunities to engage students in science alongside experienced scientists, but at large institutions, it is challenging to accommodate all students. To address and engage a larger number of students, we developed a modular laboratory course based on the course-based undergraduate research experiences model. This new course was integrated with the scientific aims of a research laboratory studying the cellular and molecular mechanisms underlying tissue regeneration in planarians. In this course, students were asked to identify genes with roles in planarian biology. Students analyzed and cloned an assigned gene, determined its expression pattern in situ and examined its function in regeneration. Additionally, we developed critical thinking and scientific communication skills by incorporating activities focused on critical concepts. Students obtained high quality primary data and were successful in completing and mastering the course learning outcomes. They benefitted by developing basic research skills, learning to perform, trouble-shooting experiments, reading and critically analyzing primary literature, and using the information to defend and explain their experimental results. Through this course, students also increased their confidence and ability to perform independent scientific research. The course was designed to make it accessible to the community to implement and adapt as appropriate in diverse institutions. Biochemistry and Molecular Biology Education Riboprobe Synthesis and Whole-Mount in situ HybridizationAntisense RNA probes were produced [23]. Briefly, DNA templates were PCR amplified from cDNA clones in pPR-T4P plasmid vectors. Antisense riboprobes labeled with digoxigenin were synthesized at 37 C. Probes were purified via ethanol precipitation and whole-mount in situ hybridization was performed manually [24] (see step by step protocol) with some modifications to fit the classroom settings. Planarians were sacrificed using a 5% N-acetyl cysteine solution prior to 548 An Undergraduate Laboratory Course Studying Planarian Regeneration

show abstract

Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias

Cited by 31 publications

References 86 publications

Ommochromes in invertebrates: biochemistry and cell biology

Ommochromes in invertebrates: biochemistry and cell biology

S-adenosylhomocysteine hydrolase regulates anterior patterning inDugesia japonica

A modular laboratory course using planarians to study genes involved in tissue regeneration

Contact Info

Product

Resources

About