The people behind the papers – Yasmine el Azhar and Ina Sonnen

Ina Sonnen (left) and Yasmine el Azhar (right)

Ina, can you give us your scientific biography and the questions your lab is trying to answer?

IS: After studying biochemistry and molecular biology, I pursued a PhD in cell biology, initially at the Max Planck Institute of Biochemistry in Munich, Germany and subsequently at the Biozentrum in Basel, Switzerland. In Erich Nigg's lab, I investigated how centrosome duplication is regulated during the cell cycle to ensure proper cell division. For my postdoctoral research, I wanted to shift focus to a multicellular perspective, aiming to understand how processes such as proliferation and differentiation are regulated within a tissue context, where cell communication ensures that ‘every cell knows what to do when and where’.

Somitogenesis is a particularly fascinating system for this purpose, as a complex network of signalling pathways ensures the accurate formation of each somite pair during embryonic development. I therefore joined the labs of Alexander Aulehla and Christoph Merten at the European Molecular Biology Laboratory in Heidelberg, Germany where I established a microfluidic system to study the function of signalling oscillations in somitogenesis. In 2018, I established my own lab at the Hubrecht Institute in Utrecht, The Netherlands. My lab now investigates how cells communicate through dynamic signalling pathways, both in the context of embryonic development, using somitogenesis as a model, and in adult tissues, focusing on the small intestine as a model system.

Yasmine, how did you come to work in the lab and what drives your research today?

YeA: I've always been fascinated by neurobiology, but it was during my Master's internship in Tristan Rodriguez's lab that I became interested in embryology. After completing my degree in regenerative medicine, I looked for a lab where I could work on neural development. That's when I joined Ina's lab, which focuses on signalling dynamics in development and homeostasis. Her approach to understanding the processes that regulate cell behaviour and tissue formation aligned with my passion for unravelling the role of signalling dynamics in the neural tube and neighbouring structures. What drives my research today is the opportunity to expand our understanding of how signalling dynamics influence development and homeostasis.

What is the background of the field that inspired your work?

IS: Over past decades, several labs have investigated the signalling pathways regulating periodic somite formation, identifying oscillations that still keep us busy today. Additionally, it has been discovered that similar oscillations occur in the developing neural tube, primarily studied in the anterior part of the embryo. Building on pioneering work by Valerie Wilson, we also know that a pool of neuromesodermal progenitors (NMPs) supplies both the presomitic mesoderm (PSM) and the neural tube. As a result, both tissues elongate and develop in parallel, with oscillations observed in each. We sought to understand how these signalling oscillations contribute to development and whether there is any coordination between the oscillations observed in the PSM and the neural tube.

YeA: The idea that signals between cells can dictate the fate of a tissue is fascinating to me. However, signalling pathways aren't just important for development, they also maintain balance in adult tissues, known as homeostasis. Therefore, I think this field holds great potential not only for understanding fundamental biological processes but also for developing therapies for diseases and tissue regeneration.

Can you give us the key results of the paper in a paragraph?

IS: In our research, we aimed to explore and compare the signalling dynamics downstream of the Notch signalling pathway in the presomitic mesoderm (PSM) and the neighbouring pre-neural tube (pre-NT). To achieve this, we created a reporter mouse line by endogenously tagging the Notch target gene Hes1. This reporter line proved to be homozygously viable and highly effective in capturing dynamic gene expression across various tissues. Leveraging this model, we quantified signalling activity in different regions of the embryonic tail, including the PSM, neural mesoderm progenitors (NMPs) and pre-NT. Additionally, we developed a single-cell tracking system using mosaic nuclear labelling in ex vivo mouse embryo cultures. This approach enabled us to measure Hes1 expression at single-cell resolution within the developing tissue. Our findings showed that PSM cells had synchronized, high-amplitude Hes1 oscillations, with signalling waves travelling across the tissue, whereas pre-NT cells exhibited noisier, less synchronized oscillations. Inhibiting Notch signalling at varying doses revealed distinct effects on Hes1 dynamics between the PSM and pre-NT, suggesting that different mechanisms drive these oscillations. These differences in Hes1 dynamics indicate varying types of information that can be transmitted by these oscillations in the adjacent tissues.

Yasmine, when doing the research, did you have any particular result or eureka moment that has stuck with you?

YeA: I did not really experience a eureka moment. Instead, it felt more like gradually completing a complex puzzle. Each experiment provided a piece of the bigger picture, and over time the connections became a bit clearer. One moment that stood out was when we saw the Hes1-Achilles signal in the confocal microscope for the first time. It was not an instant revelation, but rather the satisfaction of seeing how our ideas were coming together.

And what about the flipside: any moments of frustration or despair?

YeA: There were not any major moments of frustration or despair, but there were certainly challenges along the way. Rather than setbacks, these moments became valuable lessons. Each hurdle taught me more about my patience and problem-solving abilities. These experiences helped me better understand where I see myself in the scientific community.

IS: A significant challenge was, of course, the COVID-19 pandemic, which forced us to close the lab for 3 months just as we were getting started, with two new PhD students having recently joined. The subsequent shift to part-time work and staggered schedules delayed the project and significantly impacted scientific interactions within the lab and the broader scientific community. Fortunately, for the students there was still time afterwards to experience the excitement of attending conferences as part of the PhD trajectory.

Why did you choose to submit this paper to Development?

IS: To me, Development has always been a cornerstone in the field of developmental biology, widely read by the entire community. I also greatly value the journal's editorial work, which made me both eager and proud to publish in Development.

Yasmine, what is next for you after this paper?

YeA: Right now, I'm focused on finding a postdoc position within The Netherlands, where I can explore translational science. I'm particularly interested in applying my background in signalling dynamics to understand its role in homeostasis or regeneration within a more clinical or therapeutic context.

Ina, where will this story take your lab next?

IS: Due to technical challenges with high-resolution imaging, much of the research in the somitogenesis field has focused on studying signalling dynamics of the segmentation clock at the tissue level. Only recently have researchers begun to quantify these dynamics at single-cell resolution. Drawing on my background in biochemistry and cell biology from my PhD, I am eager to investigate somitogenesis at the single-cell and mechanistic levels. We have already taken the first steps in this direction, and I am keen to further explore how periodic signalling activity drives both somite formation and subsequent differentiation. A particularly exciting aspect of this work is the theoretical understanding of how different types of dynamics can encode information. In collaboration with Marianne Bauer (Delft University, The Netherlands), we have begun addressing this question through single-cell quantifications of dynamics, as discussed in our current publication.

Apart from this, the Hes1 reporter line has proven to be an invaluable tool in our lab. We have used it to explore Notch-driven oscillations in adult tissues, discovering that the oscillation period regulates cell type formation in the small intestine.

Ina, can you talk a bit about the work you do to promote diversity at your institute?

IS: I am highly committed to promoting diversity in science. Although some progress has been made, there remains a significant imbalance in gender, nationalities and other aspects as one advances in the career ladder – a challenge faced by nearly all research institutions. At the Hubrecht Institute, I initiated the IDEA (inclusion, diversity, equity and accessibility) committee. In collaboration with the institute and the Dutch Royal Academy, we aim to foster a more open and welcoming environment, while enhancing diversity at all levels. For example, we frequently host ‘Women in Science’ and ‘Parents in Science’ lunches, where scientists share their personal experiences, including the rewards, challenges and solutions they've encountered in their careers. These events aim to inspire and promote diversity among the next generation of scientists. Additionally, we have launched the Hubrecht Talent Program to support students from under-represented backgrounds in pursuing scientific careers.

Finally, let's move outside the lab – what do you like to do in your spare time?

YeA: In my spare time, I enjoy cooking and exploring new cuisines. I am also passionate about power yoga. Additionally, I am interested in literature that focuses on mental health, as it offers valuable insights and strategies for maintaining balance in both my personal and professional life.

IS: Outside research, I dedicate most of my free time to my family. Our children spent their early years – until they were four and six, respectively – in the EMBL community, where they naturally became part of my scientific world. They are familiar with microscopes, and it is routine for them when I go to the lab before bringing them to football. As a family, we enjoy being active outside, whether it is riding the bike or playing football. We enjoy cooking together, solving the Rubik's cube with Emilia or playing Zelda with Johannes. Now that they are getting older, the focus is gradually shifting from me bringing them to their activities to finding time for my own. Recently, I have picked up tennis again, and another goal is to start playing the guitar once more.