How was the most famous long noncoding RNA in mammals discovered? This was the subject of the round-table session “30 years of Xist/XIST discovery”, held during the 2023 X-inactivation conference in Berlin. The guests – Andrea Ballabio, Carolyn J. Brown, Neil Brockdorff and Sohaila Rastan – represented the three different teams of researchers that in three separate studies in 1991 reported the discovery of a long transcript with no coding potential associated with the inactive X chromosome, either in mouse or human. As for many other scientific discoveries, this was a journey combining hard work and dedication with serendipity. Importantly, competing teams would share data with each other – the sequences of Xist/XIST travelled across the Atlantic in floppy disks. Hosted by two PhD students, Antonia Hauth (Edith Heard’s lab) and Emmanuel Cazottes (Claire Rougeulle’s lab), the session ends with final messages to early career researchers.

To learn more about the 2023 X-inactivation conference, read the Meeting Review by Yolanda Moyano-Rodriguez and Maud Borensztein (IGMM) in Development: X-chromosome inactivation: a historic topic that’s still hot

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In the recent BSDB-the Node virtual art exhibition, Oliver Anderson’s ‘The Maw at Etna’ was selected as the Judges’ Choice in the ‘Scientific images’ category. We briefly caught up with Oliver to find out more about his research and the story behind the image.

What is your background?

I did a Bachelor of Science Advanced Research (Honours) at Monash University, majoring in Genetics and Immunology. My honours project focused on modelling metabolic disease in Drosophila. I am now undertaking a PhD at the Australian Regenerative Medicine Institute in the lab of Dr Jennifer Zenker, where I am examining microtubule dynamics in human induced pluripotent stem cells (hiPSCs). 

What are you currently researching on?
Currently, I am investigating and manipulating the microtubule cytoskeleton of hiPSCs in order to uncover the relationship between the structural aspects of pluripotent cells and their overall identity. Our current understanding of pluripotency is more heavily focused on genetic and metabolic aspects, and so microtubules are comparatively understudied at this stage of development.

Can you tell us more about the story behind your image ‘The Maw at Etna’?
This is one of my favourite immunostains of hiPSCs where I looked at alpha-tubulin. In this colony of hiPSCs, a hole of sorts was present in the centre of the colony, and I was struck by how the jagged intrusions looked like teeth, or even stalactites. Colouring the microtubules in red-yellow gave the appearance of fire, reminding me of Vulcan’s workshops below Etna mentioned in Aeneid Book VIII(Lines 416-425), where there’s wonderful imagery of living flames breathing through the forges, tended to by cyclops.

What is your favourite technique?
Anything that gets me on the (confocal fluorescent) microscope! Immunostaining has always given me beautiful samples that I can image slowly overnight, and techniques like transfection with fluorescent plasmids and live dyes often give fascinating live imaging data.

What excites you most in the field of developmental and stem cell biology?
There is such a huge amount we don’t understand about the beginnings of an organism’s life, and how the identities of cells transform over the course of development. Everywhere you look, there are so many questions unanswered, and to me that’s deeply exciting for the future.

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The webinar on 14 November 2023 was chaired by Development Senior Editor Alex Eve and featured talks from three early-career researchers studying development and disease. Below are the recordings of the talks.

Mauricio Rocha-Martins (Instituto Gulbenkian de Ciência)

Nicole Edwards (Cincinnati Children’s Hospital Medical Center)

Cecilia Arriagada (Rutger’s University)

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In this SciArt profile, we caught up with Lauren Moon, a PhD student in developmental biology who enjoys creating science-themed calligraphy and hand-painted ceramic plates.

Can you tell us about your background and what do you work on now?

I started my undergraduate degree in anatomy and developmental biology at King’s College London. Though my anatomical studies really inspired me and brought out my artistic creativity, the classes I enjoyed the most were embryology. I did a research project on zebrafish neural tube formation in my third year, which cemented my drive to pursue research in this field. I am now in the final year of my PhD, working on the mechanics of neurulation in avian embryos.

Were you always going to be a scientist?

Growing up, I was equally torn between literature and biology. I realised very quickly that whilst I wasn’t brilliant at describing what I wanted to portray in written words, expressing it in art came naturally and my passion for sketching and painting grew. For a while, I thought I could be an illustrator for manuscripts or books, creating beautiful calligraphy with art in the margins.  Biology was just as interesting and sparked my curiosity in a very different way but was more practical as a career choice (Younger me was devastated to find out there wasn’t really a call for those kind of books and manuscripts these days). As I got older and focused more on science, I realised what fascinated me the most was the small details, the underpinning bits of cell biology and tissue structures that built up to create such varied organisms, and that set me on the path to where I am now.

And what about art – have you always enjoyed it?

Art is something I think I’ve been doing for as long as I can remember, though when it started to be recognisable as anything more than broad strokes of colour and smudged outlines is a different story! I went through many different styles as my interests and the materials I had access to changed, but I settled on my love of calligraphy and playing with form and geometry in my late teens after being gifted a book on it by my great aunt, who noticed I always used to like her ornate handwriting. I do still take the chance to sit in the V&A for an afternoon to sketch their marble busts and statuary whenever I can though, there is something very relaxing about just a pencil and paper and the curve and flow of limbs and draped fabric that has stayed with me through all my stylistic changes.

What or who are your most important artistic influences?

It depends on what style or medium I’m working in really, but one of my biggest influences for the calligraphic pieces is Henry Vandyke Carter. I spent a lot of time studying Gray’s Anatomy for my undergrad, and those pieces stemmed from trying to create study aids for myself that meant I could procrastinate by doing art but still have learned something at the end. My pottery pieces, and some of my paintings and digital pieces, are more inspired by what I see down the microscope or in the lab than a specific artist or style. Confocal fluorescent images of my work are very inspiring to me; at such a high magnification translating the images to art gives an abstract view that lets me pick out shapes and colours but still connect to the biology underlying the images.

How do you make your art?

I use all sorts, but you will most often find me with either a pencil, a fountain pen or an ink brush in hand. The calligraphy is a mix of sketched outlines and ink or alcohol markers depending on the scale, with a lot of cross referencing various anatomy textbooks and personal notes and sketches. My ceramics are most often plates I picked up from homeware stores painted very painstakingly with hundreds of tiny dots using ceramic paint, based on microscopy images taken on a confocal. More recently, I have bought an artist’s tablet that plugs into my laptop and am exploring with more digital methods. So far, I have used drawing programs like Affinity for graphic designs for prints and outreach projects, as well as sculpting software to manipulate virtual clay for schematics and animations of tissue scale biological processes.

Does your art influence your science at all, or are they separate worlds?

My science very much influences my art, but the other way around? I would say it does, but perhaps not always in the most helpful way! It certainly elevates my drive to improve and push the boundaries of what my microscopy can reach, pushing me to learn more about different microscope types and builds, refractive indices and optical aberrations to achieve the greatest clarity possible in the tissues I work with. That definitely makes my eventual data collection much easier to analyse and work with, but early on did come at the cost of unfortunately huge file sizes whilst I found the balance. It also helps in thinking about how to frame my science in a way that I can easily communicate to others and where to go next; drawing a mock graphical abstract or giving a chalk talk where I need to draw out what I say helps see where the missing piece of the composition is.

The Gurdon Institute in Cambridge, where I’m based, also does a lot of public engagement and that is a part of my science that is definitely influenced by my art. One of the projects the amazing outreach team run that I got involved in is Tattoo My Science. Researchers from different labs create a design that represents their work, which is turned into temporary tattoos we can give out at outreach days. It really makes you think hard about your work and your understanding of what you do, to try and distill it into a small simple image that would appeal to (and you then have to explain to) anyone from five to one hundred and five. It also gives me a chance to bring my science out of the lab and to a new audience; last year I exhibited some of my pottery pieces at the Heong Gallery in Cambridge as part of a Fine Art prize I won and got the chance to talk about them with people from many different backgrounds.

What are you thinking of working on next?

I am (very slowly) working on creating enough of the anatomy sketches to put together an atlas with them as a long term creative goal, though once complete it will probably just sit on my shelf as a reference book and I’ll move on to the next big project! In the nearer future, I’ve been tasked with creating a logo and t shirt design for our next lab retreat, so that will be a fun departure from what I’m used to.

Find out more about Lauren:

Twitter/ X: @LDMdevbio

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“We became humans who could tell each other stories, who could imagine mutual futures, who could say, ‘I love you, and I can imagine us spending the rest of our lives together.’ We became fundamentally different perhaps as quickly as wasps acquired the ability to recognise faces.”

Rebecca Coffey

In the latest episode of the Genetics Unzipped podcast, author and science journalist Rebecca Coffey chats with us about some amazing adaptations and Darwinian delights from her book, Beyond Primates. She tells us about wasp facial recognition genes, how yeast epigenetics explain the Dutch Hunger Winter and a dinner party tale of spider cannibalism.

Genetics Unzipped is the podcast from The Genetics Society. Full transcript, links and references available online at GeneticsUnzipped.com.

Subscribe from Apple podcasts, Spotify, or wherever you get your podcasts.

Head over to GeneticsUnzipped.com to catch up on our extensive back catalogue.If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip

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Our next Development presents… webinar is on the topic of germ cell development and will be chaired by Development Editor, Swathi Arur (MD Anderson Cancer Center).

Tuesday 5 December 2023 – 15:00 GMT

The webinar will be recorded to watch on-demand. To see the other webinars scheduled in our series, and to catch up on previous talks, please visit: thenode.biologists.com/devpres

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What comes to mind when I say, “sea star”? For me, I think of easily accessible eggs that we can fertilized in vitro to make completely clear larvae that grow in a 6-well dish. Ah yes, I guess you were also thinking about snorkeling in a transparent ocean!

My name is Margherita Perillo and I am a Research Scientist at the MBL in beautiful Woods Hole right in Cape Cod. My research focuses mostly on understanding tissue and organ morphogenesis: How do individual cells group together to form complex organs? The system I chose to establish to investigate this question is the sea star Patiria miniata larva. In this short article, together with Zak Swartz (Assistant Scientist at MBL who also works with sea stars) and Jamie MacKinnon (Research Assistant from the Swartz Lab), we explain why we love this research animal.

Who works at the MBL?

The Marine Biological Laboratory is a vibrant year-round institute for research and teaching affiliated with the University of Chicago (Fig. 1). You may know us for our summer season, when we host advanced research training courses including the famous Embryology and Physiology courses, as well as visiting scientists and students from around the world, reaching a campus population of around 1,200 people. But throughout the year, MBL is home to over 30 resident faculty and laboratories across three departments, including Ecosystems Center, the Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, and the Eugene Bell Center for Regenerative Biology and Tissue Engineering. Our research community spans different length scales and disciplines, from biomedical cell biology to ecosystem-level interactions. In addition, the MBL offers immersive undergraduate courses, including the Semester in Environmental Science and the new Semester in Biological Discovery, and a brand new Ph.D. program in conjunction with the University of Chicago.  

Patiria miniata in the wild

Sea stars are echinoderms, a group of bilaterian animals that includes sea urchins, sea stars, sea lilies, brittle stars, and sea cucumbers. Because of their close relationship with vertebrates, these animals are great models to ask biomedical questions, as the basic cellular and developmental mechanisms that we study in sea stars are conserved in vertebrates (Fig. 2A). The sea star Patiria miniata (Fig. 2B) can be found all along the Pacific Coast, from Alaska to Mexico in deep and shallow waters ^1,2. We get our animals from divers in California who ship us sea stars that we keep in big tanks in the MBL Marine Resource Center. Here a team of sea star experts takes care of them to make sure they enjoy their stay and have the best possible accommodations in Cape Cod.

Life cycle: Females and male adult sea stars live in groups and when the season is right, they release their gametes out in the ocean where fertilization happens (Fig. 2C). There are gametes are in each arm and if we are lucky we find a female with six arms -extra ovaries for us! Embryos and larvae of P. miniata go through gastrulation and transform into planktonic larvae. After a few months, the larvae undergo metamorphosis to create a tiny, juvenile sea star. A remarkable feature of sea stars (and all other echinoderms) is that while their adult body has a pentameric plan, their larvae are bilateral, meaning that if we draw a line in the center of the larva there is a left and a right side, like us!

Patiria miniata in the laboratory

One of the best parts about working with sea stars is that they are incredibly easy to culture and bring through metamorphosis. A normal week in the lab begins with a trip to the Marine Resources Center (MRC) to visit our adult sea stars, check their health, and collect gonads (Fig. 3A). We carefully make a 1mm ventral incision and extract a piece of ovary; these pieces are cultured in antibiotic-treated seawater and safely kept ex-vivo for weeks at 15°C^3,4. 

When we need to expand our larval cultures, we use a dissecting needle to tease open the ovary, remove any eggs we need for the day, and add hormone to induce maturation (Fig. 3B). After fertilization, the early-stage cell divisions will happen in just a few hours. Two days later they will have developed into swimming larvae which can be transferred into 500mL boxes and fed with a red and green algal cocktail. If we change the water biweekly and continue this feeding pattern, we can observe bipinnaria larvae beginning to metamorphose within a few months. At this time we begin to feed larvae small pieces of Aquanix kelp flakes, containing spirulina, and several sources of protein. The juvenile sea stars are very low maintenance and continue to grow larger and more motile day by day!

P. miniata, an emerging system to understand organ morphogenesis

Our body is composed of many organs with diverse functions. What do they all have in common? Well, virtually all organs derive from epithelial tubes. During organogenesis these simple tubes grow, branch and elongate to make complex organs like lungs, kidneys, heart, pancreas and more. If this first step of making a tube goes wrong the embryo will develop with major birth defects with one or more organs that are shorter, have the wrong orientation in the embryo and do not function properly^5-7.

Because of the fundamental role that epithelial tubes have in building our organs a key question is: What are the mechanisms that drive proper outgrowth and elongation of epithelial tube? And what can be a good model to address this question?

While vertebrates have many, complex and highly branched organs all tightly packed together, the sea star larva has only two simple and optically clear organs: a digestive system and the hydro-vascular organ, (HVO) (Fig. 4). In my recent work, I develop two important tools that allowed us to use this new system to study how tubes form: long-term live imaging (to look at cell movements) and I set up the first CRISPR Cas9 protocols for a sea star (to perturb gene function)^8-10.

The HVO is the perfect epithelial tube: we found that it starts as a sheet of cells that bud off the digestive system (stage 1) to form two parallel tubes (stage 2) that elongate, make one branch and eventually fuse to form a looped organ (stage 3). HVO functions might be related to larval buoyancy in the water column¹¹ and I’m investigating if this is its only function.

We used the HVO as a model to define aspects of tube morphogenesis that were still poorly defined, like for instance: What drives tube elongation? We found that the FGF pathway is a major driver of tube outgrowth and that this pathway also controls branch point formation through the transcriptional factor Six1/2. Using live imaging we investigated the mechanics of tube elongation and found that cells of the growing tube actively migrate and at the same time divide to allow for tube extension and expansion. This is relevant from a biomedical perspective, as these steps are conserved with mammals ⁸.

Sea stars for fundamental reproductive biology

In the lab of Zak Swartz, we work with sea stars to explore fundamental reproductive processes from a cell biological perspective. In contrast to mammals, which undergo reproductive aging and have limited fecundity, the sea star produces millions of new oocytes throughout its (30 year+) lifespan through adult oogenesis (Figure 5A). This is a practical advantage, as having such abundant access to ovary tissue and oocytes lowers the barriers to doing our experiments. But it also fascinating biology: how do sea stars manage to continuously produce so many oocytes whereas humans are born with a limited set? Periklis Paganos is leading a project that uses single-cell genomics to define the cell type repertoire that drives this reproductive longevity, and cell biological approaches to understand how these cells interact with each other. Our goal is to define the signaling interactions and cellular states that support a long reproductive lifespan, which we hope will help inform human fertility treatments. 

Another special aspect of working with sea stars is their status as ecologically important animals. As predators and keystone species, they have an outsized impact on food webs. Like many other marine invertebrates, sea stars release their eggs directly into the seawater, with minimal protection against any fluctuations in the environment. Yet, they are fertilized and must accurately perform meiotic and mitotic processes to form an embryo under these conditions (Figure 5B). Jamie MacKinnon is asking how resilient sea star reproduction is to climate change, including variables such as temperature. By comparing eggs from different species, we aim to identify predictive measures for how marine eggs and early embryos will respond to extreme climate fluctuations. We are also working developing new genetic tools for sea stars, an effort led by Akshay Kane in our lab, and Nat Clarke at MIT, that we hope will make sea stars and other echinoderms more accessible for the research community – stay tuned!  

Patiria miniata combines a biomedically relevant phylogenetic position, genetic tools for functional analysis and a lot of oocytes and embryos available year-round -we are excited to learn more from these model organisms in the future.

This post was co-written by Margherita Perillo, Zak Swartz and Jamie MacKinnon

References

1          Ebert, T. A. Life-History Analysis of Asterinid Starfishes. The Biological Bulletin 241, 231-242, doi:10.1086/716913 (2021).

2          Morris, R. H., Abbott, D. P. & Haderlie, E. C. Intertidal invertebrates of California. Vol. 200 (Stanford University Press Stanford, 1980).

3          Swartz, S. Z. et al. Quiescent cells actively replenish CENP-A nucleosomes to maintain centromere identity and proliferative potential. bioRxiv, 433391 (2018).

4          Pal, D., Visconti, F., Sepúlveda-Ramírez, S. P., Swartz, S. Z. & Shuster, C. B. Use of echinoderm gametes and early embryos for studying meiosis and mitosis. Mitosis: Methods and Protocols, 1-17 (2022).

5          Ely, D. M. & Driscoll, A. K. Infant Mortality in the United States, 2020: Data From the Period Linked Birth/Infant Death File. Natl Vital Stat Rep 71, 1-18 (2022).

6          Baldwin, D. & Yadav, D. in StatPearls     (StatPearls Publishing

Copyright © 2023, StatPearls Publishing LLC., 2023).

7          Eitler, K., Bibok, A. & Telkes, G. Situs Inversus Totalis: A Clinical Review. Int J Gen Med 15, 2437-2449, doi:10.2147/ijgm.S295444 (2022).

8          Perillo, M., Swartz, S. Z., Pieplow, C. & Wessel, G. M. Molecular mechanisms of tubulogenesis revealed in the sea star hydro-vascular organ. Nature Communications 14, 2402, doi:10.1038/s41467-023-37947-2 (2023).

9          Oulhen, N., Pieplow, C., Perillo, M., Gregory, P. & Wessel, G. M. Optimizing CRISPR/Cas9-based gene manipulation in echinoderms. Dev Biol 490, 117-124, doi:10.1016/j.ydbio.2022.07.008 (2022).

10        Perillo, M., Swartz, S. Z. & Wessel, G. M. A conserved node in the regulation of Vasa between an induced and an inherited program of primordial germ cell specification. Dev Biol 482, 28-33, doi:10.1016/j.ydbio.2021.11.007 (2022).

11        Potts, W. T. The physiological function of the coelom in starfish larvae and its evolutionary implications. Physiol Biochem Zool 76, 771-775, doi:10.1086/381463 (2003).

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Come join us next year in France to discuss all things Neural Crest: From patient to model system and back agan.
This conference is organised by the Ph.D students of the ITN ‘NEUcrest’ aiming to highlight the works of early career researchers. We have exciting speakers, a session on living with a Neurocristopathy and a great location. Most importantly, the first 30 students to sign up to our conference, get a 50% discount. We look forward to meeting you!Scan the QR code or follow this link to register on our website: https://neucrestfinalconference.org

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In a recent Development paper, Wan-Sheng Liu and colleagues find that the cancer/testis antigen PRAMEL1 regulates spermatogonial development by inhibiting retinoic acid signaling, playing a crucial role in the proper establishment of the first and subsequent rounds of spermatogenesis. We caught up with first author Mingyao Yang to find out more about the story behind the paper.

Mingyao, what prompted you to join Wansheng’s lab at the Pennsylvania State University?                                        

During my time at China Agricultural University, I nurtured a profound fascination for reproductive biology. My passion was further ignited through my involvement in a national reproductive lab, where I delved into researching female reproductive biology. As I contemplated pursuing graduate studies in the USA, I came across Dr. Liu’s lab, in the Center for Reproductive biology and Health (CRBH) at Penn State. Although Dr. Liu’s expertise centered on male reproduction, I saw this as a distinctive chance to expand my horizons into uncharted territory. I recognized this opportunity as a platform to enrich my knowledge and skills, providing a stimulating environment for my personal and academic growth. What struck me most was Dr. Liu’s personalized mentorship. He meticulously identified my weaknesses, provided direct guidance, and helped me address each of them individually. This tailored mentorship not only inspired me but also affirmed that I was on the right path to personal growth and a successful research career.

CRBH faculties direct a dynamic and interactive graduate and postgraduate training program and conduct research in diverse areas of reproductive biology and endocrinology. Within this atmosphere, young researchers benefit from interactive learning experiences facilitated by a cohesive team of reproductive experts, engaging in cutting-edge research. In this collaborative space, students, from various labs, use shared equipment to explore diverse scientific questions. The environment fosters extensive discussions, collaborations, and mutual support among our researchers, enriching our educational journey and enhancing our research endeavors. These reasons really attracted me to Dr. Liu’s lab.

How did the project get started?

PRAME (Preferentially Expressed Antigen in Melanoma) was first discovered in melanoma cells in 1997 (Ikeda et al., 1997). Subsequent research revealed that PRAME can multiply across different chromosomes during evolution, forming a multicopy gene family in eutherian animals (Chang et al., 2011). Human, mouse, and bovine genomes contain approximately 60, 90, and 60 copies of PRAME, respectively. Since its discovery, over 500 papers have been published on the Prame family, with most focusing on cancer biology and only a few on reproduction. Our laboratory contributes to unravel the roles of the Prame family in reproduction.

In cancer biology, PRAME serves as a biomarker for various types of cancers (Epping et al., 2005; Kern et al., 2021). Its molecular function involves inhibiting the retinoic acid receptor (RAR) signaling pathway, blocking differentiation, and promoting proliferation (Epping et al., 2005). In germline development, PRAME members (PRAMEL7 and PRAMEL19) counteract retinoic acid (RA)-dependent differentiation, maintaining naïve pluripotency in embryonic stem cells (Casanova et al., 2011; Graf et al., 2017; Napolitano et al., 2020). In spermatogenesis, PRAMEF12 is known to regulate the number of spermatogonia stem cells (SSCs), although its specific molecular functions remain unstudied (Wang et al., 2019).

Previous studies in Dr. Liu’s lab revealed that PRAMEL1 expression is enriched in the testes, particularly in spermatogenic cells ranging from spermatogonia to mature spermatozoa (Liu et al., 2021; Mistry et al., 2013). Based on this information, we hypothesized that PRAMEL1 might be involved in spermatogenesis by inhibiting the RA signaling pathway.

To test this hypothesis, we generated Pramel1 conditional and global knockout mice, forming the basis for this project.

What was known about the role of retinoic acid signaling in spermatogenesis before your work?

Retinoic acid (RA) signaling plays a crucial role in male reproduction and is essential for spermatogenesis (Griswold, 2016). Animals deficient in RA exhibit spermatogonia arrest and infertility. Retinoic acid drives at least four germ cell transitions during spermatogenesis (Endo et al., 2017; Griswold, 2016). In mice, the first transition occurs a few days after birth (around postnatal day 3 (P3)), transforming prospermatogonia into three subtypes of spermatogonia: SSCs (spermatogonial stem cells), progenitors, and A1 spermatogonia (Busada et al., 2014). A1 spermatogonia continue developing to initiate the first round of spermatogenesis, progenitors initiate the second round, while SSCs prepare for subsequent rounds (Law et al., 2019). The first pulse of RA initiates this initial germ cell transition.

Additionally, during each round of spermatogenesis, RA pulses stimulate spermatogonia differentiation, spermatocyte meiosis, spermatid elongation, and the release of spermatozoa from the seminiferous epithelium.

Can you summarize the findings in a paragraph?

In this study, we examined the underlying cellular and molecular mechanisms of PRAMEL1 during spermatogenesis. We reported findings on the involvement of PRAMEL1 in the initiation and maintenance of spermatogenesis by analyzing mouse models with either global or conditional Pramel1 inactivation. We found that:

1. Pramel1 plays a crucial role in regulating RA responsiveness of cell-fate committed prospermatogonia, maintaining a balance between undifferentiated and differentiating spermatogonia during the initial round of spermatogenesis.
2. Pramel1 has a more pronounced effect on progenitors than on other subtypes of germ cells in young males. It also plays a role in maintaining undifferentiated spermatogonial populations in mature mice.
3. PRAMEL1 affects progenitor homing process during the initiation of spermatogenesis in neonatal testis.
4. Pramel1 deficiency led to an increased fecundity in juvenile males and decreased fecundity in mature males.
5. Pramel1 deficiency resulted in a regional Sertoli cell-only (SCO) phenotype during the first round of spermatogenesis, which was rescued by administration of the RA inhibitor WIN18,446, suggesting that PRAMEL1 functions as an inhibitor of RA signaling in germ cells.

Overall, our findings suggest that PRAMEL1 fine-tunes RA signaling, playing a crucial role in the establishment of the first and subsequent rounds of spermatogenesis.

Were you surprised to find that Pramel1 deficiency affected juvenile and mature mice differently?

Certainly, we were surprised by these findings, as we did not anticipate the divergent function of PRAMEL1 in young animals compared to older ones.

Interestingly, a novel concept has emerged indicating that the first round of spermatogenesis constitutes a distinct program separate from the subsequent rounds (Law et al., 2019; Yoshida et al., 2006). During the first round, sperms are produced at a juvenile age, whereas the subsequent rounds of spermatogenesis occur during mature age. The initial A2 spermatogonia, transitioning directly from prospermatogonia in response to the first RA pulse, drives the first round of spermatogenesis. In contrast, the subsequent rounds of spermatogenesis originate from spermatogonial stem cells (SSCs). Our results provide compelling evidence supporting the idea that the mechanisms underlying the first round and subsequent rounds of spermatogenesis are different.

Did you have any particular result or eureka moment that has stuck with you?

During this work, I often felt like walking in a maze. There are too many unsolved mysteries during spermatogenesis. However, fresh results and inventive ideas, whether derived from literature, expert insights, or our own discussions, served as beacons of guidance, illuminating our path, and bringing moments of clarity amidst the intricate complexity.

One of the exciting moments was when we obtained the whole-mount immunofluorescence (IFS) results following RA treatment. These results revealed that the RA inhibitor successfully rescued the regional SCO phenotype in the young gKO testis. This outcome strongly suggested that PRAMEL1 acts as an inhibitor of RA signaling during spermatogenesis. Typically, my advisor, Dr. Wansheng Liu, and I often have different interpretations or perspectives regarding my results. However, this time, he wholeheartedly agreed with me when we examined the original results, and our shared enthusiasm underscored the significance of our findings.

And the flipside: were there any moments of frustration or despair?

Certainly, graduate school, especially for international students like me, came with its fair share of frustrating moments. One such instance involved the extensive immunofluorescence staining required for our research paper. Initially, the staining procedures didn’t yield high-quality results, possibly due to issues with our protocol or the antibodies we were using. I persisted in optimizing our protocol, conducting the staining repeatedly in an attempt to improve the outcomes. Simultaneously, I experimented with numerous antibodies sourced from different companies. Complicating matters, our funding was limited at that time, requiring us to approach these companies and request free samples of antibodies, which we tested one by one. The journey to completing this project was arduous, but it was also incredibly motivating to witness the quality of results improving gradually with each attempt.

What’s next for this story? And personally, Mingyao, what is next for you after this paper?

In this study, we understand the role of PRAMEL1 during spermatogenesis while our previous study has revealed? the function of PRAMEX1 in testis. To gain a better understanding of the role of PRAME family during spermatogenesis, we have successfully generated a Pramel1/Pramex1 double knockout mice. Thus, the next of this story is to figure out the interaction of the two different members of Prame family during spermatogenesis.

For me, I will further explore the mystery during spermatogenesis in the lab of Dr. Oatley (one of our co-authors in this paper) in Washington State University.  My career goal is to become an independent investigator researching the mechanisms that underpin spermatogenesis. My hope is that the outcomes of my research program will be translated to solutions for male infertility that impacts humans, domestic animals, and wildlife. Infertility is a significant concern that affects a substantial number of people worldwide, with approximately 20% of couples facing difficulties conceiving a pregnancy. Through my research in male reproductive biology, I aim to contribute to the development of innovative solutions and interventions to address the male side of infertility. This involves investigating the underlying causes of male infertility, treatment options, and improving assisted reproductive technologies. By gaining a deeper understanding of reproductive processes and disorders, I hope to make meaningful contributions to improving fertility outcomes and enhancing the quality of life for individuals and families facing fertility challenges.

Reference:

Busada, J. T., Kaye, E. P., Renegar, R. H., & Geyer, C. B. (2014). Retinoic acid induces multiple hallmarks of the prospermatogonia-to-spermatogonia transition in the neonatal mouse. Biology of Reproduction, 90(3), 1–11. https://doi.org/10.1095/biolreprod.113.114645

Casanova, E. A., Shakhova, O., Patel, S. S., Asner, I. N., Pelczar, P., Weber, F. A., Graf, U., Sommer, L., Bürki, K., & Cinelli, P. (2011). Pramel7 mediates LIF/STAT3-dependent self-renewal in embryonic stem cells. Stem Cells, 29(3), 474–485. https://doi.org/10.1002/stem.588

Chang, T., Yang, Y., Yasue, H., Bharti, A. K., Retzel, E. F., & Liu, W. (2011). The Expansion of the PRAME Gene Family in Eutheria. 6(2). https://doi.org/10.1371/journal.pone.0016867

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To showcase the variety of interests and artistic talents among the developmental biology community, the Node and the British Society for Developmental Biology (BSDB) have jointly organised a virtual art exhibition, to accompany the European Developmental Biology Congress that happened in September 2023.

Thank you to all the talented people who submitted their artwork and to everyone who has visited the art exhibition so far. The exhibition is open until the end of November 2023.

We asked you, the Node community, to vote for your favourite artwork from the exhibition. We also asked a panel of judges from the BSDB and The Company of Biologists to choose their favourite — and the results are now in!

Category: Scientific images

Judges’ choice

Judges’ choice runner-up and People’s choice

Category: Science-inspired art

Judges’ choice and People’s choice

Judges’ choice runner-up

Crocheted models of embryonic development
Tahani Baakdhah (Krembil Research Institute, University of Toronto)
Crocheted model of 5 days, 1 week, 2 weeks and 2 months gestational embryonic development.

(Click on individual image to see the full size version)

Category: Art by Scientists

Judges’ choice

Judges’ choice runner-up

People’s choice

(10 votes)

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