The people behind the papers – Yuuta Moriyama and Carl-Philipp Heisenberg Free

Yuuta Moriyama (and his two daughters, Kaede and Ann, left) and Carl-Philipp Heisenberg (right).

Carl-Philipp, what questions is your lab trying to answer?

C-PH: The central question we seek to address is how embryo morphogenesis is orchestrated across biological scales. To tackle this, we take an interdisciplinary approach at the intersection of biology and physics, aiming to elucidate how mechanical and chemical factors engage in dynamic feedback loops that drive morphogenetic processes. Our primary model systems are zebrafish and ascidians, though we have recently expanded our work to include non-model organisms such as copepods.

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

YM: I was originally fascinated by the beauty of embryonic development, which inspired me to enter the field of developmental biology. As I progressed in my research, I became increasingly interested in how the physical properties of individual cells and cell collectives contribute to embryogenesis – and ultimately, to evolution. Motivated by this curiosity, I joined the lab of Dr Heisenberg at the Institute of Science and Technology Austria. Today, I pursue my research with the aim of understanding how microscopic dynamics at the single-cell level give rise to the global body plan of the embryo.

Tell us about the background of the field that inspired your work

YM: Gastrulation has long been a central focus in developmental biology, with many fascinating phenomena and conceptual breakthroughs discovered and proposed by outstanding researchers over the years. Among them, the work by Iimura and Pourquié stands out as a milestone in understanding the expression and function of Hox genes during this process (Iimura and Pourquié, 2006). They showed that Hoxb cluster genes are expressed in a temporally collinear manner in the epiblast, regulating the timing of ingression into the hypoblast. As a result, cells that ingress earlier contribute to more anterior somites, while those that ingress later are allocated to more posterior ones – in essence, temporal information is translated into spatial patterning through gastrulation. I read this paper as an undergraduate student and it left a deep impression on me. Although I didn't immediately pursue this topic in my own research, the fascination with this phenomenon has always remained in the back of my mind. When I later joined Dr Heisenberg's lab, I felt it was finally time to address this question. My starting point was to examine whether the temporally collinear expression and function of Hoxb genes during gastrulation are conserved in zebrafish. Then, if so, I wanted to explore the underlying cellular dynamics and mechanics. Zebrafish, with their advantages for live imaging, seemed like the ideal model to investigate this in detail.

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

YM & C-PH: In our study, we first demonstrate that Hoxb cluster genes are expressed in a temporally collinear manner at the blastoderm margin, the region where epiblast cells undergo ingression into the hypoblast, in zebrafish gastrulation. Furthermore, we showed that the expression of these Hoxb genes regulates the timing of cell ingression: functional perturbation using morpholino-mediated knockdown and generation of knockout lines revealed that inhibition of individual Hoxb genes impairs cell ingression at the onset of their expression. Moreover, premature expression of posterior Hoxb genes led to a similar inhibition of early gastrulation-stage ingression as observed upon loss of function of more anterior Hoxb genes. Furthermore, we showed that the timing of cell ingression is translated into a spatial pattern along the anterior-posterior axis after gastrulation. How, then, do Hoxb genes regulate cell ingression? High-temporal-resolution imaging revealed that dynamic membrane blebbing, as an expression of increased cell surface fluctuations, plays a crucial role in this ingression process. In summary, we found that Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations and subsequent cell blebbing during gastrulation, which, in turn, establish the anterior-posterior patterning of the embryos.

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

YM: I was at a loss for words when I first observed the distribution pattern of the transplanted donor cells within the host embryo under the microscope – it was simply beautiful. Similarly, I've often found myself captivated by the beauty of life as seen through the microscope – whether it was watching individual cells bleb and ingress or observing the collective behaviour of cell populations and the embryo as a whole.

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

YM: It was a great challenge for me when I had to return to Japan in the middle of this project, which forced an interruption of my research in Dr Heisenberg's lab. Establishing my own lab in Japan was also particularly demanding, especially because I was affiliated with a Department of Physics, where the infrastructure for biological research was not readily available. Setting up essential equipment – such as a zebrafish system and advanced microscopy setups – required considerable time and posed substantial logistical difficulties. Despite these circumstances, Dr Heisenberg continued to encourage me, held regular discussion about the research and consistently supported me throughout. Thanks to his unwavering support, we were able to bring this project to completion and I'm truly delighted that we could share our findings through a publication in Development.

Why did you choose to submit this paper to Development?

YM: Development covers a broad range of topics in developmental biology and publishes many interesting papers, which I always enjoy reading with each issue. I had never published my own research in Development before but had always hoped to do so one day – which is why I decided to submit this work to Development.

C-PH: Importantly, Development is published by a not-for-profit publisher, setting it apart from commercial publishers that dominate the scientific publishing landscape with profit-driven models, and thus, needs as much support as possible from the community.

Yuuta, what is next for you after this paper?

YM: Moving forward, I aim to dissect the molecular mechanisms by which Hox genes control bleb formation at the cellular level. In parallel, I am intrigued by the possibility that Hox-driven cell behaviours during gastrulation may vary across species. Building on this idea, I plan to explore the evolutionary implications of these differences through comparative analysis of developmental processes in different species.

Carl-Philipp, where will this story take your lab next?

C-PH: Understanding the molecular and cellular mechanisms that drive cell internalisation during gastrulation remains an open and challenging question. We still do not know why mesoderm and endoderm progenitors initiate inward movement, how Hox genes regulate this process or how it is coordinated with changes in cell polarisation, migration and adhesion. Moreover, it is unclear how morphogen-mediated specification of mesoderm and endoderm cell fates leads to internalisation, and how spatial confinement and embryo geometry shape this behaviour.

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

YM: On my days off, I often spend time outdoors with my daughters – going to the park for picnics, catching insects and running around together. As for my own hobbies, I'm passionate about music: I enjoy playing instruments, collecting records and listening to them. That passion for music also reminds me of my time in Dr Heisenberg’s lab – one of the things I look back on fondly is playing string quartet music together with him. I hope that when my daughters grow older, we'll be able to play music together and go record hunting as a family.

C-PH: In my free time, I enjoy spending quality time with my family, playing the cello in the evenings, and going for regular runs and bike rides. I find that being outdoors – especially in the company of friends – is both grounding and invigorating. Immersing myself in nature helps clear my mind, providing the mental space and balance needed to stay creative, focused and enthusiastic in the lab.