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)
Talk and Q&A by Mauricio Rocha-Martins
Nicole Edwards (Cincinnati Children’s Hospital Medical Center)
Talk and Q&A by Nicole Edwards
Cecilia Arriagada (Rutger’s University)
Talk and Q&A by Cecilia Arriagada (1 votes) Loading...
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.
Red neural tube – Painted ceramic plate, after a confocal image of a memRFP transgenic chick anterior neural tube undergoing closure.
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.
Kidney relations – Calligraphic representation of the structures that abut the posterior of the kidneys, colour coded for muscle (green), bone (orange) and vasculature. Alcohol markers on toned paper.
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.
Anatomical surfaces of the pelvis, Ink on toned paper.
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.
Painted ceramic plate, after a confocal image of a chick embryo showing the closing neural folds. Sample was stained for nuclei (DAPI, blue) and neural fate (Sox2, green).Painted ceramic plate, after a confocal image of a chick embryo showing the closed neural tube and somites. Sample stained for nuclei (DAPI, blue), neural fate (Sox2, green) and actin (Phalloidin, red).
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.
Calligraphic representation of the brachial plexus in situ. Alcohol markers on toned paper.
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.
Selection of temporary tattoo designs based on projects within the lab. Left to right, they are 1) overlaid stages of primary neural tube closure, 2) Example of culture technique using filter paper and 3) a project involving the role of Nodal in zebrafish development. Graphical tablet using Affinity Designer.
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.
“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.
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
Gabriele Zaffagnini (Centre for Genomic Regulation) ‘Why don’t oocytes get Alzheimer’s?’
Diego Sainz de la Maza (University College London) ‘Somatic cells support germ cell survival by shuttling glycolytic products’
Güneş Taylor (Francis Crick Institute) ‘The role of FOXL2 in pregranulosa cell specification within the vertebrate ovary’
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
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.
Figure 1. The MBL Campus. Credit Marine Biological Laboratory
Patiria miniatain 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!
Figure 2. A) Phylogenetic tree showing relationship of echinoderms to other deuterostomes. There are five families of echinoderms and they all have a 5-fold symmetry (only a coincidence?). B) Adults Patiria miniata come in different colors that range from red, to purple, orange or beige (Picture of one of our sea stars at MBL, Credits Margherita Perillo). C) P. miniata life cycle, from eggs or sperm released from adults to larval stages that eventually undergo metamorphosis and transform into a tiny sea star juvenile (Cartoon modified from Perillo et. al, 2023).
Patiria miniatain 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°C3,4.
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!
Figure 3. A) We keepthe sea starP. miniata in big tanks with sea water at 15°C in the MRC facility at MBL. B) Jamie working with sea star ovaries under a dissection scope.
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 properly5-7.
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.
Figure 4. A) A live sea star larva where digestive system and hydro-vascular organ (HVO) are highlighted. These are the only two organs of this organism and follow a stereotypical growth. B) Stages of HVO development (laminin staining).
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!
Figure 5. A) Adult female sea star spawning out thousands of eggs, visible as the orange material emanating from between the arms. B) A summary of cell division processes between fertilization and the first embryonic cleavage that we study in our lab.
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.
1 Ebert, T. A. Life-History Analysis of Asterinid Starfishes. The Biological Bulletin241, 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 Rep71, 1-18 (2022).
6 Baldwin, D. & Yadav, D. in StatPearls (StatPearls Publishing
7 Eitler, K., Bibok, A. & Telkes, G. Situs Inversus Totalis: A Clinical Review. Int J Gen Med15, 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 Communications14, 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 Biol490, 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 Biol482, 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 Zool76, 771-775, doi:10.1086/381463 (2003).
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
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.
Excerpts from previous paper (Kern et al., 2021)Excerpts from previous paper (Liu et al., 2021)
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:
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.
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.
PRAMEL1 affects progenitor homing process during the initiation of spermatogenesis in neonatal testis.
Pramel1 deficiency led to an increased fecundity in juvenile males and decreased fecundity in mature males.
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.
The role of PRAMEL1 during the establishment of spermatogenesis. (A) A model for RA responsiveness in three germ cell lineages in the wild-type and Pramel1– deficient mice (for details, see paper). The critical time points during germ cell development in mice are indicated below the model. (B) A proposed model for the establishment of stages I to stage XII of the seminiferous epithelial cycle in a neonatal wild-type and Pramel1 gKO testis. A1 and A2, A1 and A2 spermatogonia; Pl, preleptotene spermatocyte; ProSG, prospermatogonia; SCO, Sertoli cell-only; SSC, spermatogonial stem cell.
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.
Whole-mount immunofluorescent staining with TRA98 (red) antibodies on seminiferous tubules. White dashed lines outline SCO regions. Nuclei are counterstained with DAPI (blue).
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
Endo, T., Freinkman, E., De Rooij, D. G., & Page, D. C. (2017). Periodic production of retinoic acid by meiotic and somatic cells coordinates four transitions in mouse spermatogenesis. Proceedings of the National Academy of Sciences of the United States of America, 114(47), E10132–E10141. https://doi.org/10.1073/pnas.1710837114
Epping, M. T., Wang, L., Edel, M. J., Carlée, L., Hernandez, M., & Bernards, R. (2005). The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell, 122(6), 835–847. https://doi.org/10.1016/j.cell.2005.07.003
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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
The Maw at Etna Oliver Anderson (Australian Regenerative Medicine Institute) In this image, microtubules are shown in red/yellow, and nuclei in white. Cells rush to fill an opening in the colony, with their jagged flame-like microtubules roaring into the centre like the devouring forge-flames of Cyclopean Etna. (Aeneid Book VIII: Lines 416-425) Human induced pluripotent stem cells, imaged using a Zeiss LSM780 confocal microscope. Cells are labelled with DAPI (white), and immunostained for alpha-tubulin (red-yellow).
Judges’ choice runner-up and People’s choice
The backbone of stem cell derived embryos Christoph Markus Haefelfinger (California Institute of Technology) The cytoskeletal structure of preimplantation embryos demonstrated in a reconstruction of a stem cell derived mouse blastoid. After fixation, the structure was immunostained for f-actin (phalloidin, grey) and the inner cell mass (Oct4, red), then imaged.
Category: Science-inspired art
Judges’ choice and People’s choice
Klimt-olotl Elad Bassat (Research Institute of Molecular Pathology, IMP) The decision of Axolotls to stay in water rather than metamorphose. As I am in Elly Tanaka’s lab in Vienna I drew it in the style of the Austrian Gustav Klimt.
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
Living Water Brent Foster (Whitney Laboratory for Marine Bioscience) Ink drawing of an octopus. When I see these creatures glide across a surface, I almost think of them as living water.
Judges’ choice runner-up
Castle of Dreaming Dragons Morag Lewis (King’s College London) This began as a small pencil sketch in 2019, and grew into a multipage creation over the year until it was finished in June 2020. It was inked digitally, then printed in sections and painted using watercolours.
People’s choice
Nautilus Brent Foster (Whitney Laboratory for Marine Bioscience Chalk drawing of a nautilus.
The webinar on 25 October 2023 was chaired by Development Associate Editor Irene Miguel-Aliaga (Imperial College London) and features three early-career researchers studying metabolism and development. This webinar coincided with the completion of Development’s Special Issue: Metabolic and Nutritional Control of Development and Regeneration. Below are the recordings of the talks.
Maria Fernanda (Nanda) Forni (Yale University)
Talk and Q&A by Maria Fernanda (Nanda) Forni
Hidenobu Miyazawa (EMBL Heidelberg)
Talk and Q&A by Hidenobu Miyazawa
Siamak Redhai (DKFZ)
Talk and Q&A by Siamak Redhai (1 votes) Loading...
Luka Jarc, Manuj Bandral, Elisa Zanfrini, Mathias Lesche, Vida Kufrin, Raquel Sendra, Daniela Pezzolla, Ioannis Giannios, Shahryar Khattak, Katrin Neumann, Barbara Ludwig, Anthony Gavalas
John R. Klem, Tae-Hwi Schwantes-An, Marco Abreu, Michael Suttie, Raeden Gray, Hieu Vo, Grace Conley, Tatiana M. Foroud, Leah Wetherill, CIFASD, C. Ben Lovely
Surag Nair, Mohamed Ameen, Laksshman Sundaram, Anusri Pampari, Jacob Schreiber, Akshay Balsubramani, Yu Xin Wang, David Burns, Helen M Blau, Ioannis Karakikes, Kevin C Wang, Anshul Kundaje
Adam David Langenbacher, Fei Lu, Luna Tsang, Zi Yi Stephanie Huang, Benjamin Keer, Zhiyu Tian, Alette Eide, Matteo Pellegrini, Haruko Nakano, Atsushi Nakano, Jau-Nian Chen
Jeannine Basta, Lynn Robbins, Lisa Stout, Michelle Brennan, John Shapiro, Mary Chen, Darcy Denner, Angel Baldan, Nidia Messias, Sethu Madhavan, Samir V. Parikh, Michael Rauchman
Vi Pham, Livia Sertori Finoti, Margaret M. Cassidy, Jean Ann Maguire, Alyssa L. Gagne, Elisa A. Waxman, Deborah L. French, Kaitlyn King, Parith Wongkittichotee, Xinying Hong, Lars Schlotawa, Beverly L. Davidson, Rebecca C. Ahrens-Nicklas
Archana Kamalakar, Brendan Tobin, Sundus Kaimari, Afra I. Toma, Irica Moriarity, Surabhi Gautam, Pallavi Bhattaram, Shelly Abramowicz, Hicham Drissi, Andrés J. García, Levi B. Wood, Steven L. Goudy
Bongjun Kim, Yuanjian Huang, Kyung-Pil Ko, Shengzhe Zhang, Gengyi Zou, Jie Zhang, Moonjong Kim, Danielle Little, Lisandra Vila Ellis, Margherita Paschini, Sohee Jun, Kwon-Sik Park, Jichao Chen, Carla Kim, Jae-Il Park
Shoichiro Takeishi, Tony Marchand, Wade R. Koba, Daniel K. Borger, Chunliang Xu, Chandan Guha, Aviv Bergman, Paul S. Frenette, Kira Gritsman, Ulrich Steidl
Alice Santambrogio, Yasmine Kemkem, Thea L. Willis, Ilona Berger, Maria Eleni Kastriti, Louis Faure, John P. Russell, Emily J. Lodge, Val Yianni, Rebecca J. Oakey, Barbara Altieri, Stefan R. Bornstein, Charlotte Steenblock, Igor Adameyko, Cynthia L. Andoniadou
Elvira H. de Laorden, Diana Simón, Santiago Milla, María Portela-Lomba, Marian Mellén, Javier Sierra, Pedro de la Villa, María Teresa Moreno-Flores, Maite Iglesias
Ethan Tietze, Andre Rocha Barbosa, Bruno Henrique Silva Araujo, Veronica Euclydes, Hyeon Jin Cho, Yong Kyu Lee, Arthur Feltrin, Bailey Spiegelberg, Alan Lorenzetti, Joyce van de Leemput, Pasquale Di Carlo, Tomoyo Sawada, Gianluca Ursini, Kynon J. Benjamin, Helena Brentani, Joel E. Kleinman, Thomas M. Hyde, Daniel R. Weinberger, Ronald McKay, Joo Heon Shin, Apua C.M. Paquola, Jennifer A. Erwin
Manon Jaffredo, Nicole A. J. Krentz, Benoite Champon, Claire E. Duff, Sameena Nawaz, Nicola Beer, Christian Honore, Anne Clark, Patrik Rorsman, Jochen Lang, Anna L. Gloyn, Matthieu Raoux, Benoit Hastoy
Rosalie Sinclair, Minmin Wang, Zaki Jawaid, Jesse Aaron, Blair Rossetti, Eric Wait, Kent McDonald, Daniel Cox, John Heddleston, Thomas Wilkop, Georgia Drakakaki
David Bolumar, Javier Moncayo-Arlandi, Javier Gonzalez-Fernandez, Ana Ochando, Inmaculada Moreno, Ana Monteagudo-Sanchez, Carlos Marin, Antonio Diez, Paula Fabra, Miguel Angel Checa, Juan Jose Espinos, David K Gardner, Carlos Simon, Felipe Vilella
Daniel Frank, Maria Bergamasco, Michael Mlodzianoski, Andrew Kueh, Ellen Tsui, Cathrine Hall, Georgios Kastrappis, Anne Kathrin Voss, Catriona McLean, Maree C Faux, Kelly Rogers, Bang Tran, Elizabeth Vincan, David Komander, Grant Dewson, Hoanh Tran
Martina Jabloñski, Guillermina M. Luque, Matías D. Gómez-Elías, Claudia Sanchez-Cardenas, Xinran Xu, Jose Luis de la Vega-Beltran, Gabriel Corkidi, Alejandro Linares, Victor X. Abonza Amaro, Dario Krapf, Diego Krapf, Alberto Darszon, Adan Guerrero, Mariano G. Buffone
Bernard Y. Kim, Hannah R. Gellert, Samuel H. Church, Anton Suvorov, Sean S. Anderson, Olga Barmina, Sofia G. Beskid, Aaron A. Comeault, K. Nicole Crown, Sarah E. Diamond, Steve Dorus, Takako Fujichika, James A. Hemker, Jan Hrcek, Maaria Kankare, Toru Katoh, Karl N. Magnacca, Ryan A. Martin, Teruyuki Matsunaga, Matthew J. Medeiros, Danny E. Miller, Scott Pitnick, Sara Simoni, Tessa E. Steenwinkel, Michele Schiffer, Zeeshan A. Syed, Aya Takahashi, Kevin H-C. Wei, Tsuya Yokoyama, Michael B. Eisen, Artyom Kopp, Daniel Matute, Darren J. Obbard, Patrick M. O’Grady, Donald K. Price, Masanori J. Toda, Thomas Werner, Dmitri A. Petrov
Zhisong He, Leander Dony, Jonas Simon Fleck, Artur Szałata, Katelyn X. Li, Irena Slišković, Hsiu-Chuan Lin, Malgorzata Santel, Alexander Atamian, Giorgia Quadrato, Jieran Sun, Sergiu P. Paşca, J. Gray Camp, Fabian Theis, Barbara Treutlein
Michael J Cotton, Pablo Ariel, Kaiwen Chen, Vanessa A Walcott, Michelle Dixit, Keith A Breau, Caroline M Hinesley, Kasia Kedziora, Cynthia Y Tang, Anna Zheng, Scott T Magness, Joseph Burclaff
Nusayhah Hudaa Gopee, Ni Huang, Bayanne Olabi, Chloe Admane, Rachel A Botting, April Rose Foster, Fereshteh Torabi, Elena Winheim, Dinithi N Sumanaweera, Issac Goh, Mohi Miah, Emily Stephenson, Win Min Tun, Pejvak Moghimi, Ben Rumney, Peng He, Sid Lawrence, Kenny Roberts, Keval Sidhpura, Justin Englebert, Laura Jardine, Gary Reynolds, Antony Rose, Clarisse Ganier, Vicky Rowe, Sophie Pritchard, Ilaria Mulas, James Fletcher, Dorin-Mirel Popescu, Elizabeth FM Poyner, Anna Dubois, Andrew Filby, Steven Lisgo, Roger A Barker, JONG-EUN PARK, Roser Vento-Tormo, Phuong Ahn Le, Sara Serdy, Jin Kim, CiCi Deakin, Jiyoon Lee, Marina T Nikolova, Neil Rajan, Stephane Ballereau, Tong Li, Josh Moore, David Horsfall, Daniela Basurto Lozada, Edel A O’Toole, Barbara Treutlein, Omer Bayraktar, Maria Kasper, Pavel Mazin, Laure Gambardella, Karl Koehler, Sarah Teichmann, Muzlifah Haniffa
Henry Tat Quach, Spencer Farrell, Kayshani Kanagarajah, Michael Wu, Xiaoqiao Xu, Prajkta Kallurkar, Andrei Turinsky, Christine Bear, Felix Ratjen, Sidhartha Goyal, Theo J Moraes, Amy Wong
Patrice Pottier, Malgorzata Lagisz, Samantha Burke, Szymon M. Drobniak, Philip A. Downing, Erin L. Macartney, April Robin Martinig, Ayumi Mizuno, Kyle Morrison, Pietro Pollo, Lorenzo Ricolfi, Jesse Tam, Coralie Williams, Yefeng Yang, Shinichi Nakagawa
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