Here are the highlights from the current issue of Development:

pancRNAs in early development

Promoter-associated noncoding RNAs (pancRNAs) are a class of long noncoding RNAs, transcribed from bidirectional promoters and thought to be involved in promoting expression of the gene transcribed from the opposite strand. Takuya Imamura and colleagues (p.910) now set out to investigate the prevalence and potential functions of such pancRNAs during early mouse development. Focussing on the 2-cell stage, when the major wave of zygotic gene activation (ZGA) occurs, they use directional RNA-seq technology to identify several hundred pancRNAs upregulated in concert with their cognate coding RNA. To assess the potential functional relevance of this co-regulation, the authors analyse three candidates, including Il17d/pancIl17d. In each case, siRNA-mediated knockdown of the pancRNA impairs expression of the mRNA and also prevents the normal DNA demethylation associated with gene upregulation at the ZGA. They further find that depletion of pancIl17d leads to defects in blastocyst survival and in embryonic stem cell colony formation – phenotypes that can be rescued by the provision of recombinant IL17D. Although the mechanisms by which pancRNAs act remain poorly understood, these data provide evidence for an important physiological role for pancRNAs in promoting expression of their partner mRNAs during early development.

Uncovering neurogenic potential of striatal astrocytes

Adult neurogenesis in mammals is generally confined to specific regions where astrocytic cells produce particular neuronal types throughout life. Outside these areas, the capacity for neurogenesis is limited. However, on p.840, Paolo Peretto, Federico Luzzati and co-workers provide evidence that striatal astrocytes can be activated to a neurogenic program in an adult mouse model of Huntington’s disease. Following treatment with the toxin quinolinic acid to induce a lesion, the authors observe the appearance of proliferating progenitors and neuroblasts. Fate-mapping experiments identify local striatal astrocytes as the source of this neurogenic program. Importantly, neurogenesis is only observed upon lesion, suggesting that these astrocytes are normally quiescent but possess latent neurogenic potential upon damage. Further analysis is required to understand the programs regulating this neurogenesis, to determine the final fate of the newly born neuroblasts and to assess whether a similar phenomenon might exist in humans. However, these data open the possibility of harnessing the neurogenic potential of striatal astrocytes for therapeutic purposes.

Timing degradation to tune development

A key issue in developmental biology is how particular processes are coordinated in time: for example, what determines when development of a particular organ starts and how quickly it proceeds? Jennifer Nemhauser and colleagues explore this problem in Arabidopsis, using auxin-mediated regulation of lateral root development as a model (p. 905). Specifically, they investigate the consequence of manipulating the degradation rate of the auxin-responsive transcriptional co-repressor IAA14, the mutation of which is known to affect lateral root formation. Using a synthetic biology approach, the authors generate several versions of IAA14 that show varying degradation kinetics upon auxin stimulation, and then generate transgenic plants expressing each version from the wild-type promoter. They find that both the density and timing of lateral root emergence inversely correlates with IAA14 stability: more stable variants show fewer lateral roots and these roots take longer to initiate. IAA14 is part of a large family of Aux/IAA repressors and these data suggest that regulating the degradation rate of these proteins could act as a tunable timer for developmental progression in plants.

Getting to the heart of heart cell identity

Cardiac progenitor cells differentiate into multiple cell types that make up the functional heart: cardiomyocytes (CMs), smooth muscle cells (SMCs), endothelial cells (EDCs) and fibroblasts. These lineage decisions can be modelled by differentiation of embryonic stem cells (ESCs), but it is not fully clear how closely these in vitrosystems reflect in vivo developmental progression, or how much variability there is within the progenitor population – either in culture or in the embryo. On p.846, Sean Wu and co-workers use single-cell quantitative PCR and lineage-tracing assays on embryonic and adult mouse cardiac cells, as well as mouse ESCs differentiated down the cardiac lineage, to define a gene expression signature for each of the various cell types. Amongst the wealth of data generated, a number of key findings emerge. Firstly, the authors find that ESC-derived CMs closely resemble embryonic and neonatal endogenous CMs, but adult CMs diverge. Secondly, embryonic and ESC-derived cardiac progenitors show different potential: both generate CMs, but embryonic cells can differentiate to EDCs while ESC-derived progenitors produce SMCs. These data demonstrate the power of the single-cell profiling approach and provide valuable insights into lineage choices during cardiac development.

Asymmetric division and fate in the retina

In many systems, neural progenitor cells divide asymmetrically to generate a self-renewing progenitor and a committed neuron. How is this fate segregation controlled, and what defines the balance of proliferation and differentiation? Using live imaging in the developing zebrafish retina, Lucia Poggi and colleagues (p. 832) address these questions, focussing on the role of Anillin – a protein involved in cytokinesis – in the cell divisions that generate retinal ganglion cells (RGCs). By following individual divisions, the authors find that Anillin is itself asymmetrically inherited between daughter cells, and directs the asymmetric inheritance of actin and the polarity protein Par3. Cells with reduced Anillin levels tend to divide symmetrically, generating two RGCs rather than a progenitor and a RGC. Globally, this results in a retina with more RGCs. The authors further show that anillin expression is itself regulated by the RGC fate determinant Ath5, suggesting that there may be feedback loops involving Ath5 and Anillin that control the balance of proliferation and differentiation. How Anillin acts to regulate asymmetric division and fate choice remains unclear, but this technically challenging study demonstrates the importance of this protein in the control of neurogenesis in the retina.

PLUS…

Neural development and regeneration: it’s all in your spinal cord

The latest advances in the field of spinal cord development and regeneration were discussed at a recent EMBO workshop entitled ‘Spinal cord development and regeneration’, which was held in Sitges, Spain, in October, 2014. Here, Catherina Becker and Ruth Diez del Corral provide a review of the workshop. See the Meeting Review on p. 811

 

A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation

Decades of work have identified the signaling pathways that regulate the differentiation of chondrocytes during bone formation, from their initial induction from mesenchymal progenitor cells to their terminal maturation into hypertrophic chondrocytes. Here, Elena Kozhemyakina, Andrew Lassar and Elazar Zelzer review how multiple signaling molecules, mechanical signals and morphological cell features are integrated to activate a set of key transcription factors that determine and regulate the genetic program that induces chondrogenesis and chondrocyte differentiation. See the Review on p. 817

 

Beautiful imaging of zebrafish development

This issue’s featured movie shows the development of a zebrafish, from early embryo to larval stage, imaged using a combination of optical tomography and SPIM. Read the Techniques and Resources article by Huisken and colleagues here.

 

 

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Alongside my main role as community manager of the Node I am also Development’s online editor, and one of my responsibilities is writing press releases. I recently wrote a press release on a Development paper that received some media attention, and I was surprised by the way the story was covered. The articles ranged from balanced reports to over-hyped pieces. This experience highlighted some of the pitfalls of the way science stories reach the media, so I thought I would share my thoughts on it here.

We don’t often write press releases on Development papers. Most of our papers are primarily of interest to the scientific community, but we do occasionally publish work with a clear broader impact. One such article was a recent paper by Rebecca Robker and colleagues. It examined at the cellular level why the oocytes of obese mice are less fertile and showed that oocytes from these mice have high levels of ER stress, leading among other things to loss of mitochondria in the offspring and reduced fertility. In addition, the authors were able to show that these effects can be reversed before conception by treating the obese mice with ER stress inhibitors (one of which is currently in human clinical trials for diabetes). You can read the paper here and the ‘In This Issue’ summary in Development here. Although basic research, this work touches on two issues of interest to the general public- obesity and fertility. Both we and The University of Adelaide press office wrote press releases on the article (here and here).

A little background for those of you not familiar with press releases. Journalists work to tight deadlines and don’t have the time to go through the table of contents of all journals to find news-worthy content. Instead, they rely on press releases produced by journals or institutes. These are very short articles that answer the big 5 W’s: who, what, where, when and why. Journalists will wade through lists of press releases every day in search of a good story, so press releases often have an attention-grabbing title and are written in such a way that the most important information is right at the beginning. A press release is not the final news article on the work, but rather aims to interest the journalist in the story and encourage them to investigate further.

I don’t have a lot of experience writing press releases, but my strategy is to focus on a single, main message. I decided that in this case the press release should focus on the fact that the damage to the oocytes was revertible. Having written the piece, I sent it to the corresponding author for approval and to ask for appropriate quotes. This is important as it gives the author the opportunity to check that the press release reflects the work accurately. The final version was then emailed to our press contacts and posted on EurekAlert! (a widely-used press release site) in advance of the publication date, under a strict embargo.

The paper by Robker and colleagues reached some high profile websites and newspapers, but the quality of the reporting was quite varied. The Science magazine news website and The Scientist wrote good pieces on the work. They described the main experiments conducted and discussed the limited implications of the work to humans. In both cases the journalists involved contacted other researchers in the field to provide an independent expert opinion. At the other end of the scale was the piece published by the Daily Mail, a UK-based tabloid. The Daily Mail article over-hyped the work, claiming that a cure for obesity-related fertility problems had been found. Importantly, at no point was it mentioned that the work was conducted in mice. Not all generalist newspapers misrepresented the work though, as the balanced article released by the Mail & Guardian in South Africa attests. As some of the comments left by readers of the Daily Mail show, misrepresenting scientific work has implications for the way scientists, and indeed doctors, are perceived, and some of the coverage appeared to suggest that an off-the-shelf drug is already available to help obese mothers. The NHS (UK National Health Service) website wrote an excellent piece attempting to dispel these misconceptions, providing a detailed explanation of the research as well as discussing how the work had been misrepresented in the media.

At a time when we are increasingly aware of the importance of communicating science to the public, newspapers and news sites are a fantastic way to reach a wide audience. Scientists have to play an active part to help ensure that the work is represented accurately, but once a press release is out there, they have no control over how their study is described. One thing you can do is to work hard with the press officers at your institute or journal to produce the best press release possible. In addition, be available for interviews and use this as an opportunity to steer reporters in the right direction (more advice on this here). For me, this has been a story with mixed blessings: though disappointing to read inaccurate reporting, it is heartening to see that journalists appreciate the importance of basic research and its potential implications for human health.

We would love to hear your thoughts on communicating with the press, so leave a comment below!

Image credit: Macarena Gonzalez

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POSTDOCTORAL POSITIONS are available to study the cellular and molecular mechanisms controlling the development of the lymphatic vasculature and the visual system using available mouse models and 3D self-organizing stem cells and iPS. Highly motivated individuals who recently obtained a PhD. or MD degree and have a strong background in stem cells and molecular and developmental biology are encouraged to apply. Interested individuals should send their curriculum vitae, a brief description of their research interests, and the names of three references to:

Guillermo Oliver, Ph.D (guillermo.oliver@stjude.org)
Member
Department of Genetics
St. Jude Children’s Research Hospital
332 N. Lauderdale
Memphis, TN 38105
USA
www.stjude.org/departments/oliver.htm

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Stockholm University, Sweden, invites applications for one postdoctoral position in the laboratory of Professor Mattias Mannervik at the Department of Molecular Biosciences, The Wenner-Gren Institute (http://www.su.se/mbw/research/research-groups/integrative-biology/group-mannervik). The position is scheduled to start as soon as possible.

Transcriptional coregulators are proteins that facilitate communication between transcription factors and the basal transcription apparatus, in part by affecting chromatin through post-translational modification of histones. As such, they contribute to generation of cell-type specific gene regulatory networks and epigenetic control of animal development (see Mannervik et al. Science, 284, 606-609). This laboratory is using molecular, genetic, and transgenic approaches in Drosophila melanogaster to elucidate the molecular mechanisms of transcription and chromatin regulator function during development. The project will involve genome-wide analysis by ChIP-seq technology and CRISPR/Cas9-mediated genome engineering.

The position is available immediately and requires a recent Ph.D. as well as extensive experience in molecular biology techniques. The successful applicant should have a high-quality publication record, and motivation to study underlying mechanisms of gene regulation in development. The position will be funded with a fellowship, and includes health insurance.

Stockholm University is one of the largest and most prominent universities in Sweden, located in the nation’s capital city, beautifully surrounded by the first national city park in the world. For further information, see http://www.su.se/english/ and http://www.academicstockholm.se/

Application: 
Applications marked with reference number SU FV-0499-15 should be submitted electronically as a single PDF file to mattias.mannervik@su.se and to registrator@su.se. The application deadline is March 8, 2015

Applications should comprise the following:

1) a personal statement describing research interests (1-2 paragraphs), research experience (1–2 paragraphs) and career goals (1-2 paragraphs)

2) curriculum vitae

3) bibliography

4) names, e-mail adresses, and phone numbers of three references

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We are looking for a PhD student with experience in Hippo/YAP cell biology, molecular biology and mouse handling, and a keen interest in dermatology and regeneration. Department of Anatomy, School of Medical Sciences, UNSW, Sydney. For inquiries and/or applications, please contact Dr. Annemiek Beverdam (A.Beverdam@unsw.edu.au).

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Senior Post-Doctoral Research Associate in Nanoformulation Safety Assessment

(to commence May 4^th 2015)

University of East Anglia, Norwich, UK, in collaboration with Procarta Biosystems Ltd, Norwich, UK , Consorzio Interuniversitario Per Lo Sviluppo Dei Sistemi A Grande Interfase (CSGI), Florence, Italy and Nanovector, Turin, Italy, are looking to recruit an experienced researcher. The position will be based at University of East Anglia, for 13 months. The position is funded by the European Union under Framework 7 SP3-PEOPLE program, Support for training and career development of researchers (Marie Curie), “Industry-Academia Partnerships and Pathways” (IAPP), Grant Agreement number 612338, DNA TRAP – Delivery of Nucleic Acid-Based Therapeutics for the Treatment of Antibiotic-Resistant Pathogens.

The recruit should have knowledge and experience of performing safety tests on drugs or nanomaterials using in vitro cell culture models and/or in vivo models such as Xenopus laevis or zebrafish.

The candidate should have a PhD degree in cell biology, molecular biology, nanomedicine or developmental biology or at least 4 years full-time equivalent research experience post-degree. Background in Drug development will be particularly appreciated. Moreover, ability to collaborate in a highly multidisciplinary environment is absolutely required (molecular biologists, chemists, industry and academic partners, materials scientists). The candidate should have excellent interpersonal skills and experience of training or supervising others.

The candidate should not have resided or carried out his/her main activity in the UK for more than 12 months in the 3 years immediately prior to his/her recruitment. Short stays in the UK, such as holidays, are not taken into account. This position offers generous remuneration and includes a monthly mobility allowance, based on the family status of the candidate. Applications are invited from all nationalities, and are not restricted to the European Union countries.

Eligible candidates will be selected based on scientific skill and relevance of their research experience to the project and their ability to meet the criteria regarding mobility and research experience described above. This is an equal opportunity position.

These Marie Skłodowska-Curie Fellowship appointments are offered an annual salary of the Sterling equivalent of €78,624 per annum, plus an additional monthly Mobility Allowance of €1344 for candidates who are married or supporting a dependent child, or €941 without. These amounts are subject to UK employment tax and national insurance, including employer’s national insurance contributions and any other employment costs such as employer pension contributions.

Informal enquiries can be sent to: christopher.j.morris@uea.ac.uk or grant.wheeler@uea.ac.uk

Closing date for applications: 6^th March 2015

Proposed interview date: 23^rd March 2015

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Here is February’s round-up of some of the interesting content that we spotted around the internet!

News & Research:

– A new technique called ‘expansion microscopy‘ makes tissues swell up in order to observe structures at higher resolution.

– Mary Lyon, the mouse geneticist who proposed the theory of X-chromosome inactivation, died last December. Obituaries on her life and research can be read in the Guardian and Nature.

– How English became the only language of science– an interesting historical overview in Aeon.

– A recent blog post argued that papers should be written with more style and beauty. Do you agree?

– Plant developmental biologist Caroline Dean is the winner of the 2015 FEBS | EMBO Women in Science Award

– ‘Fly Room‘ is a feature film on the relationship between one of T H Morgan’s students and his daughter, and provides an interesting insight into the early years of fly genetics. The next screening will be at Janelia Farm!

– An opinion piece in Science compared the maternity/paternity leave support for postdocs in the US and in Europe.

– ‘In the 1970s, radical scientists thought they could change the world’- thought provoking article in Mosaic.

– ‘Not your average technician‘- article on Nature News  on technicians with unusual jobs.

– An interesting article in the Guardian discussed the interplay between science and science fiction.

– Christiane Nüsslein-Volhard, the grande dame of developmental biology– article by the Lindau Nobel Laureate meeting

– The Sanger institute released a new website with a variety of educational resources about the genome.

Weird & Wonderful:

– ‘Thank you ants for helping me science‘- a cute project shows that the scientific method can be applied by all age groups!

– This xkcd comic explores the gut (macro) fauna.

– Following the success of the Lego Research Institute set, two more science lego projects you can vote for: HMS Beagle and Scientists in History.

– We spotted this fantastic poster/t-shirt from last year’s SDB meeting:

The #devbio of a cup of coffee: Fantastic poster/t-shirt from last year’s SDB meeting! pic.twitter.com/DpwmK2ZVUx

— the Node (@the_Node) January 8, 2015

 

 
Beautiful & Interesting images:

– We spotted a couple of science cakes in the last few weeks: this muscle fibers cake and a cell division cake

– Is it snowing where you are? Here are some Nobel Prize snowflakes to cheer up your day!  

Nobel Prize snowflake patterns! For a sciency Christmas RT @Ri_Science http://t.co/IH3yLKqJ59 pic.twitter.com/LiH71Q1jWN — the Node (@the_Node) December 18, 2014

Videos worth watching:

– What is Evo-Devo and how did this field come to be?- Arkhat Abzhanov explains in this video!

– Is your PI away all the time? This video shows that you are not alone.

– And the Manchester Fly Facility produced this great educational video on the history and importance of Drosophila in biomedical research.

Keep up with this and other content, including all Node posts and deadlines of coming meetings and jobs, by following the Node on Twitter

(3 votes)

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 Phreatichthys andruzzii, lateral view (left), frontal view (right)

Adaptations of some fish species to their environment can be most peculiar, especially within cave dwelling kinds. The so called troglomorphisms slowly turn these fish into almost grotesque looking creatures with no eyes, lost pigments and no scales on the one hand, but with enhanced alternative sensory systems on the other hand.

Cavefish of different orders have been found in cave systems from Mexico to China, all revealing different degrees of adaptations to their life underground. One astonishing example for extreme troglomorphism is represented by the species Phreatichthys andruzii. These fish have been living for about 2 million years in complete darkness in a place, where one would not expect swimming fish at all: under the Somalian desert. Due to this total isolation from surface streams, adult P. andruzzii exhibit full regression of eyes, scales and pigments (see pictures). Remarkably, and similar to the well studied Mexican cavefish Astyanax mexicanus, eyes start to develop during embryogenesis following the stereotypic patterning of eye field determination and subsequent evagination, forming the optic cups. Despite the effort, apoptosis is initiated in later stages and ultimately leads to the loss of the organ. Both species have clearly been evolving separately from each other in two different continents, but concerning the eye loss, the outcome is very similar.

Thus in order to investigate, whether the development is similar on the molecular level as well, or if there maybe are differences, we started an intensive in situ hybridization (ISH) study of key transcription factors and components of regular vertebrate eye development (based on zebrafish and medaka). In the cavefish Astyanax it has been shown that midline signalling of shh (sonic hedgehog) is expanded in early developmental stages, when the eye field is forming, which leads to dysregulation of subsequent transcription factor expression and guidance. When we analysed the early developmental stages of P. andruzzii, we could not detect any obvious deviation of transcription factor patterning and corresponding eye formation. Moreover, when we looked at later stages, we even detected an establishing ciliary marginal zone (CMZ), the teleost stem cell niche of the eye. This observation is further supported by anti-PCNA immunohistochemistry, revealing active proliferation in the CMZ. Taken together, until the onset of further differentiation, the early patterning and formation of the Phreatichthys eyes proceed as in surface species like D. rerio.

From this stage onwards, normal morphogenesis of the vertebrate eye is accompanied by highly stereotypic differentiation of retinal progenitor cells (RPCs), which results in the characteristic layering of the eye. Retinal ganglion cells (RGCs) are born first, 
followed by horizontal, amacrine and bipolar cells and the late-born rod and cone photoreceptors, as well as non-neuronal Müller glia cells. Since no discrete layering of the cavefish retina has been observed at any time point, we studied this developmental phase by addressing cell type specific transcription factor genes with ISH. Our data revealed that only the first born RGCs are established, but not maintained. Detailed analysis of processes of these neurons also revealed no connection to the optic tectum, rendering them functionless. This disruption of the typical differentiation cascade consequently inhibits generation of further cell types and no layering occurs.

Furthermore, we detected massive apoptotic events spreading over the entire neuroretina from this time point onwards, which might very well be triggered by the dysregulated differentiation, in order to protect the eye against aberrant proliferation. Thus, we speculate that a simple differentiation block building on intrinsic control mechanisms elegantly eliminates the Phreatichthys retina.

In comparison to Astyanax, a different strategy is being followed to eradicate the eye during embryogenesis, which specifically blocks differentiation and layering of the neuroretina. In several Astyanax populations this layering proceeds, but apoptosis eventually intervenes, too. By studying these diverse modes of eye degeneration within cavefish species, light can be shed on the different developmental checkpoints and how they are controlled in normally developing vertebrate eyes.

Photographs courtesy of Luca Scapoli.
Stemmer, M., Schuhmacher, L., Foulkes, N., Bertolucci, C., & Wittbrodt, J. (2015). Cavefish eye loss in response to an early block in retinal differentiation progression Development, 142 (4), 743-752 DOI: 10.1242/dev.114629

(7 votes)

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One postdoctoral and one technician positions, both fully funded for 3 years, are available in the laboratory of Dr. Natalia Sanchez-Soriano at the Institute of Translational Medicine, Department of Cellular and Molecular Physiology, University of Liverpool, UK. We are seeking highly motivated, collaborative, interactive but independent candidates to study fundamental microtubule- and transport-related mechanisms underlying the formation and maintenance of axons and synapses, and their links to neurodegeneration. Ideally, applicants should be trained in neuro- and/or cell biology, molecular biology and imaging, and have experience with the model organisms Drosophila. For more information about our group see https://sanchezlab.wordpress.com

The laboratory benefits from a highly interactive scientific environment in the Department of Cellular and Molecular Physiology at the University of Liverpool, and an outstanding neurobiology community in the Northeast of England. In addition, Liverpool offers broad cultural and recreational opportunities. Interested candidates should email Natalia Sanchez-Soriano (Natalia1 [at] liverpool.ac.uk) with a statement of interest together with a CV.

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Time for the slightly delayed third round of images from the 2013 Woods Hole embryology course! Below you will find 4 beautiful images from the course. Choose the one you would like to see in the cover of Development by voting on the poll at the end of the post (you can see bigger versions by clicking on the images). The poll is set up to allow only one vote per person, so please stick to this rule to give all the images a fair chance!

Voting will close noon GMT on March the 2nd.

1. Scanning electron micrograph of a black scale from the butterfly, Papilio blumei. Visible is the elaborately sculptured lattice between the microrib-covered ridges. Acting in concert with melanin inside the scales, these scale cuticle nanostructures are thought to contribute to making these scales exceptionally black by trapping light through internal reflection. Imaged on a Zeiss Supra40VP SEM. Distance between ridges is approximately 2 µm. This image was taken by Lara Linden (Duke University, USA).

2. Blastoderm stage Drosophila melanogaster embryo. In situ hybridization for the 5’ end of Scr in yellow, Antp in blue (from the P1 promotor, 5’ in the first intron), and a previously uncharacterized lincRNA in pink. Imaged on a Leica SP8 confocal. This image was taken by Wiebke Wessels (James Cook University, Australia).

3. Living embryo of the little skate (Leucoraja erinacea) sitting atop its yolk at approximately ten weeks of development. Imaged on a Zeiss Discovery.V20. This image was taken by Mary Colasanto (University of Utah, USA) and Emily Mis (Yale University, USA).

4. Wing of the Blue Mountain Swallowtail (Papilio ulysses). The blue scales seen here contain no blue pigment, rather the physical interaction of light with cuticle-based nanostructures of the scale creates a metallic blue color. Imaged on a Zeiss Discovery.V20 with image planes stacked using Helicon Focus. This image was taken by Emily Mis (Yale University, USA) and Misty Riddle (UC Santa Barbara, USA).

(4 votes)

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