We introduced our Outstanding Paper Prize in 2022 (Briscoe et al., 2023). Each year since then, reviewing the papers shortlisted by our editors, and selecting the finalists and overall winner has become something of a highlight. This year in particular, with the scientific enterprise feeling under more pressure than usual, it's been a real pleasure to be able to focus on some of the fantastic studies that featured in the journal in 2024.
Last year, 287 Research Articles and Reports, and Techniques and Resources papers we published were eligible for the prize. From these, our editors shortlisted a set of 19 for consideration. In selecting the finalists and eventual winners, we were looking for papers that we thought would make a real impact on their respective fields, and that took conceptually and/or technically innovative approaches; in short, papers that exemplified the best of developmental biology and what Development is all about.
We recognise that any decision based on ranking papers will be somewhat subjective, and so – before announcing the winners – we'd like to take a moment to recognise all our contributors from 2024. Publishing in Development is something you can and should be proud of; we know that you put a lot of work into your papers, and we hope that your experience of publishing with us has been a positive one (though please do tell us what we can do to improve). We thank you for choosing Development over the myriad of other choices available to you.
You can find the full shortlist of papers in our subject collection online (https://journals.biologists.com/dev/collection/17876/Outstanding-Paper-Prize-2024). These papers feature species from across the tree of life, employ a diverse set of experimental and computational approaches, and explore a broad range of scientific questions – from the evolution of muscle cell multinucleation to the tissue-scale response to dietary stress. From this great group of papers, we chose three standout studies, which will feature in a special edition of our Development presents webinar on 28 May. These three papers are:
Long-range formation of the Bicoid gradient requires multiple dynamic modes that spatially vary across the embryo by Thamarailingam Athilingam, Ashwin V. S. Nelanuthala, Catriona Breen, Narain Karedla, Marco Fritzsche, Thorsten Wohland and Timothy E. Saunders (doi: 10.1242/dev.202128)
Fetal brain response to maternal inflammation requires microglia by Bridget Elaine LaMonica Ostrem, Nuria Domínguez-Iturza, Jeffrey A. Stogsdill, Tyler Faits, Kwanho Kim, Joshua Z. Levin and Paola Arlotta (doi: 10.1242/dev.202252)
Large-scale CRISPR screen reveals context-specific genetic regulation of retinal ganglion cell regeneration by Kevin Emmerich, John Hageter, Thanh Hoang, Pin Lyu, Abigail V. Sharrock, Anneliese Ceisel, James Thierer, Zeeshaan Chunawala, Saumya Nimmagadda, Isabella Palazzo, Frazer Matthews, Liyun Zhang, David T. White, Catalina Rodriguez, Gianna Graziano, Patrick Marcos, Adam May, Tim Mulligan, Barak Reibman, Meera T. Saxena, David F. Ackerley, Jiang Qian, Seth Blackshaw, Eric Horstick and Jeff S. Mumm (doi: 10.1242/dev.202754)
Of these, we selected the paper by Bridget Ostrem and colleagues as our overall winner. Many congratulations to the authors of all three papers, and particularly to Bridget – who wins a £1000 cash prize in recognition of her fantastic contribution to the journal.
So what appealed to us about these papers? The study from Athilingham et al., which came to us from Review Commons, stood out as a great example of the power of combining highly quantitative experimental approaches with mathematical modelling to bring new understanding to an old problem in the field, namely, how a robust morphogen gradient can be generated dynamically and over a long distance. Although the Bicoid gradient in the Drosophila embryo has been known about since the late 1980s, it is still not fully understood how the gradient can be formed, maintained and interpreted with such high precision. This paper adds significantly to our understanding of this question, and provides a framework that may be valuable for other studies of morphogen signalling. As one referee remarked, the work is ‘a beautiful example of dynamical studies in vivo’.
Our second finalist, from Emmerich et al., demonstrates the power of CRISPR-based genetic tools, combined with single-cell technologies, to provide insights into cellular behaviours in vivo. One referee sums up the paper as ‘a very important manuscript in the field of retinal regeneration that significantly extends our understanding of a very underappreciated aspect of retinal regeneration, namely, how the retina determines which cell type to replace’. By ablating retinal ganglion cells (RGCs) in the zebrafish larva and following their recovery, the authors were able to identify factors that specifically affect RGC regeneration, highlighting the degree to which the cellular response to injury varies according to the precise nature of that injury.
Finally, turning to our overall winner, the study from Ostrem et al. that addresses an important but poorly understood question – how maternal infection affects fetal brain development. The authors explore this question using a mouse model of maternal immune activation (MIA) and single-cell sequencing analysis, and identify a key role for microglia in mediating the fetal response in the brain. Perhaps most strikingly, the transcriptional changes identified in microglia persist postnatally, which may provide a mechanistic basis for the fact that maternal infection is associated with an increased prevalence of neuropsychiatric disorders. In addition, the paper provides a substantive resource for the community in terms of characterising the molecular heterogeneity of microglia both in untreated mice and the MIA model. These data, according to one of the referees, ‘are extremely relevant to our understanding of the molecular underpinnings of the pathobiology induced by MIA and will lead to many hypotheses about the role of microglia in the process’. We selected this paper as the overall winner thanks to its use of modern approaches to provide substantive insights into both normal development and disease biology. You can find out more about the story behind the paper in Box 1.
Box 1. The story behind ‘Fetal brain response to maternal inflammation requires microglia’
A brief interview with Bridget Ostrem, Nuria Dominguez and Paola Arlotta.
What was the motivation behind this study?
BO, ND & PA: Maternal inflammation and infections during pregnancy are associated with increased risk of future neuropsychiatric disorders in affected children. Associated conditions include schizophrenia and autism spectrum disorder. We wanted to understand how the fetal brain is impacted by maternal inflammation at a cellular level.
In the paper, you show that microglia mediate the effects of maternal immune activation on other cell types in the developing brain, but did not explore how this might be occurring. Have you since gained any insights into this mechanism?
PA: Broadly, we're really interested in understanding the mechanisms underpinning the effects of in utero insults (including but not limited to MIA) on the developing brain. Ultimately, we believe that a combination of in vitro research, animal model work and human studies is needed. In our more recent work, we used a three-dimensional cell culture system (brain chimeroids) to ask how a variety of cell types in the developing brain are affected by in utero insults (Anton-Bolaños et al., 2024). We started this work by testing the teratogens ethanol and valproic acid, which are also associated with adverse neuropsychiatric outcomes, instead of immune stimulants, given the limited immune response capabilities of brain chimeroids. We identified cell type-specific effects on progenitor cells, and on excitatory and inhibitory neurons, of exposure to these teratogens. Interestingly, the effects varied in cell types from different human genetic backgrounds, and we believe the same may be true of the response to inflammation. This finding underscores the importance of work by other groups to develop personalized medicine approaches to preventing and treating disease.
The consequences of maternal immune activation on the microglia transcriptome are still visible in juvenile offspring. What do you think this tells us about the long-term consequences of infection during pregnancy, and how might this impact potential therapies for maternal infection-related neuropsychiatric conditions?
BO: Our findings may help to explain the results of epidemiological studies in humans linking maternal inflammation to adverse neuropsychiatric outcomes. Our observation of persistently altered microglial transcriptional profiles in juvenile mice suggests, firstly, that fetal microglia-directed interventions may be able to promote lasting brain recovery, and, secondly, that even if fetal intervention is not possible, therapeutics that target microglial function or gene expression during childhood could benefit patients with a history of fetal brain insults.
Where are you taking this work next?
PA & ND: This project has led to many additional exciting questions - there is so much to do in this area! We are now working to understand common molecular pathways that may explain similar clinical phenotypes of different insults to the developing fetal brain. Bridget has also started her own laboratory (see below) and is moving her research into therapeutic development for related fetal and neonatal neurological conditions.
Bridget – can you tell us a little about your career history and future plans?
Prior to completing my postdoctoral fellowship in the Arlotta laboratory, I completed an MD and PhD at the University of California, San Francisco, in the laboratory of Dr Arnold Kriegstein, and a clinical residency in Pediatric Neurology. I also completed a clinical fellowship in Maternal-Fetal Neurology. I am now an Assistant Professor of Neurology at UCSF. My laboratory is focused on understanding, preventing and developing better treatments for acquired brain injury in babies. I also see patients with neurological conditions in clinic and in the hospital.
Together, these papers – and the broader shortlist – exemplify the diverse range of studies that Development publishes, and showcase the exciting research being conducted across our community. The value of the papers we publish is thanks not only to our authors but also to our peer reviewers, who ensure that the work is rigorously but constructively reviewed prior to acceptance. We are hugely grateful for the time they put in, and thank all our reviewers of the past 12 months for their work. A full list of reviewers is provided in the supplementary information.
While times are challenging for many researchers at present, we are excited by the current state and future prospects for developmental biology – given the range of experimental and theoretical approaches, and the diverse set of in vivo and in vitro systems, available to the community. If you'd like to be in with a chance of winning next year's Outstanding Paper Prize, we welcome your submission and look forward to working with you on your paper.
