In this Perspective, our 2024 Pathway to Independence Fellows provide their thoughts on the future of their field. Covering topics as diverse as plant development, tissue engineering and adaptation to climate change, and using a wide range of experimental organisms, these talented postdocs showcase some of the major open questions and key challenges across the spectrum of developmental biology research.

Marcella Birtele

The rapid advancement of stem cell technologies has revolutionized our approach to studying human development and disease. Among the most exciting developments has been the generation of brain organoids – three-dimensional, self-organizing structures that recapitulate key features of the human nervous system (Lancaster et al., 2013; Kadoshima et al., 2013). The power of stem cell-derived neural organoids lies in their ability to dissect the cellular diversity (Velasco et al., 2019) and architecture of the human nervous system in a dish, and in their accessibility for manipulation and analysis. Cutting-edge techniques, such as single-cell transcriptomics and lineage-tracing genome editing, can be readily applied to these models, allowing a comprehensive understanding of gene expression dynamics, cell-cell interactions and signalling pathways during neural development.

Moreover, the use of patient-derived induced pluripotent stem cells (iPSCs) enables the generation of personalized disease models, offering insights into the pathogenesis of neurological conditions with genetic underpinnings. For example, in my postdoctoral work (Birtele et al., 2023), I investigated the role of an autism spectrum disorder (ASD) associated gene, SYNGAP1, in human cortical neurogenesis. In a patient-derived cortical organoid model of SYNGAP1 haploinsufficiency, we identified defects both in the cytoskeletal organization of apical radial glia and in their mode of division – leading to disrupted neurogenesis. These findings reveal an important function for SYNGAP1 at early stages of development, providing a new framework for understanding the pathophysiology of ASD.

By harnessing the self-organizing potential of pluripotent stem cells together with induced patterning strategies, researchers can now generate region-specific organoids, such as those representing the cerebral cortex, midbrain, thalamus, cerebellum and spinal cord (Zhou et al., 2024), with the overarching goal of understanding the diversity and function of neural progenitors, neurons and glia in development and disease. One current area of research focus is the development of more-sophisticated organoid systems that recapitulate the interactions between different brain regions. For example, the generation of assembloids, which combine organoids representing distinct brain structures, can provide insights into the formation and function of neural circuits. In addition, recent advances now allow the integration of vascular cells and microglia into neural organoids, enabling the study of neurovascular coupling and neuroimmune interactions in health and disease.

While advances in neural organoid technology have predominantly focused on the central nervous system, as the field of neural organoids continues to evolve, several exciting avenues for future research are emerging, such as studying the peripheral nervous system. This growing area of research is what I want to focus on in my future lab. Pioneering efforts have been made to unravel the cellular and molecular composition of the human enteric nervous system (ENS) (Drokhlyansky et al., 2020). With our knowledge of the diversity and organization of the ENS steadily expanding, advances in generating organoids that accurately recapitulate its development and function have become paramount. By leveraging organoid technology to model the intricate cellular and molecular dynamics of the ENS, I hope to gain invaluable insights into its development, function and potential dysregulation in disease states. Specifically, I aim to build on my experience in cortical organoids and neuronal physiology by investigating how ENS organoids could facilitate the exploration of the bidirectional communication between the central and peripheral nervous systems, unveiling previously unrecognized interactions and their implications for neurological disorders.

As the field of organoids continues to push boundaries, the refinement of protocols and the characterization of peripheral nervous system organoids holds the potential to uncover novel therapeutic strategies and to enhance our understanding of the human nervous system as an integrated interconnected network.

Martina Cerise

Our lives are intricately affected by plants in myriad ways – whether they are an ornament in our home, something to enjoy in our gardens or a tasty food on our plate, plants account for 80% of the Earth's biomass (Bar-On et al., 2018). The organs of all land plants develop from discrete populations of undifferentiated stem cells. Studies over recent decades have revealed that several stem-cell niches (SCNs) are formed from embryogenesis onwards, and these regulate the development of the above- and below-ground organs that determine plant morphology. In particular, three main groups of SCNs are involved in the formation of different plant tissues: the shoot apical meristem (SAM) controls the formation of all aboveground organs, such as leaves and flowers; the root apical meristem (RAM) promotes the development of all underground tissues, such as roots; and cambium cells regulate vascular morphogenesis and radial stem development both above and belowground (Eljebbawi et al., 2024; Greb and Lohmann, 2016). Throughout the life of the plant, the maintenance and regulation of SCNs is crucial, as new organs are constantly being produced and growing from these cells.

The gene regulatory networks involved in SCN maintenance have been extensively studied in the model plant Arabidopsis and have described a mechanism by which the position of cells within meristematic tissues plays a prominent role in determining their identity. In all three niches, a basic organising module consisting of two groups of cells controls SCN maintenance during the plant life cycle. The first group, the inductive niche, contains signalling cells that produce non-cell-autonomous homeodomain transcription factors that move into the neighbouring stem cells and maintain them in an undifferentiated state. The second group, which contains the stem cells themselves, produces small peptides that activate a negative-feedback loop in the inductive niche to repress the expression of the homeodomain transcription factors and prevent the overproliferation of stem cells (Greb and Lohmann, 2016).

Several genes have been identified that regulate this SCN homeostatic loop under standard conditions (Eljebbawi et al., 2024); more recently, the effect of different environmental cues on stem-cell maintenance has revealed that, under stress, key regulators of this tissue organisation change their expression to respond to different stimuli and prevent cells in the SCN from differentiating (Landrein et al., 2018; Wenzl and Lohmann, 2023; Zeng et al., 2024). Moreover, pioneering studies in Arabidopsis have identified changes in SAM morphology and organisation associated with floral transition (Bertran Garcia de Olalla et al., 2024; Kinoshita et al., 2020) and proliferative arrest (Balanzà et al., 2023), stages when the plant starts and stops to flower, respectively. In particular, the morphological changes that occur within the apical SCN during floral transition determine the final architecture of the inflorescence and, thus, the number of flowers and fruits produced by the plant. Despite the extensive knowledge of the gene regulatory networks that control floral transition (Kinoshita and Richter, 2020), the interplay between inflorescence establishment and SCN maintenance is poorly understood. Reflecting the complexity of SCN regulation during the plant-life cycle, I have shown that both the inductive niche and the stem cell region change in size and shape during floral transition (Bertran Garcia de Olalla et al., 2024 – a paper on which I am co-first author). My future work aims to understand why these morphological changes in the SCN are important for the acquisition of inflorescence architecture and to identify the gene regulatory networks that promote these changes specifically during the floral transition. These studies will increase our understanding of how SCN homeostasis changes during the plant life cycle, and offer the possibility of applying these resources to related crops to modify inflorescence shape and crop yield.

Lydia Djenoune

Initially described about 300 years ago, cilia – hair-like microtubule-based organelles of several micrometers in length present in most animal cells – were originally believed to function exclusively in cellular propulsion. They have since then been linked to a plethora of sensory and signalling events, as well as to the pathogenesis of numerous diseases, commonly referred to as ciliopathies. However, their functions in many systems remain largely unexplored.

In vertebrates, one of the systems in which ciliary signalling has been the subject of particular attention is in left-right (LR) patterning. Cilia are essential for this process as mutations affecting their structure or function lead to defective LR patterning. During embryogenesis, symmetry breaking is initiated in the LR organizer (LRO), a transient, evolutionarily conserved, ciliated epithelium where cilia generate and transduce leftward flow of extra-embryonic fluid to induce asymmetry (Nonaka et al., 1998). Both ciliary signalling and flow are crucial for proper LR development. Nonetheless, how flow is transduced by cilia to signal asymmetric signalling cascades remains unclear. Over the years, two main models (which are not necessarily mutually exclusive) have been proposed: the ‘morphogen flow’ hypothesis, suggesting that LRO flow asymmetrically distributes short-lived molecules across the LRO (Tanaka et al., 2005), and the ‘two-cilia’ model that proposes that LRO flow driven by motile cilia initiates a calcium influx in cells on the left side of the LRO via activation of polycystin ion channels in primary cilia that function as shear flow mechanosensors (McGrath et al., 2003; Yoshiba et al., 2012). Combining new optical and genetic tools, I recently demonstrated that cilia are calcium-mediated mechanosensors that convert the LRO flow via the polycystin channel Pkd2 to instruct LR asymmetry (Djenoune et al., 2023). However, there are still many open questions about how Pkd2 and cilia sense and translate flow into morphogenetic signals in the LRO – and hence into downstream morphological asymmetry – and whether cilia sustain equivalent functions in other organs.

Abnormal blood flow through the heart and vasculature at early developmental stages is associated with abnormal cardiac development. This clearly indicates that flow is crucial in shaping the early heart, meaning there must be a mechanism at play enabling the heart to sense and respond to fluid flow. Cilia are an obvious candidate for mediating the effects of blood flow in the heart, but, thus far, research on the role of cilia during cardiogenesis has focused primarily on LR patterning of the early heart rather than on later developmental stages. I am interested in understanding the role of cardiac cilia within the developing heart beyond their contribution to shaping its LR asymmetry. Primary cilia are present in the mouse embryonic heart and their absence leads to intracardiac structural defects, such as malformations of the endocardial cushions and a compact myocardium (Slough et al., 2008). Despite a growing number of studies that have reported developmental defects in the heart associated with ciliopathies (Li et al., 2015), a consensus on the role of cardiac cilia has not yet been reached. They have been linked to haemodynamic mechanosensation, valvulogenesis and myocardial regeneration (Li et al., 2020), but more needs to be done to reveal how primary cilia sense and respond to different cues during the various stages of cardiogenesis. To achieve this, distinguishing between their role in the LRO and their functions in embryonic and adult cardiac tissues will be key.

Developmental biology has never been as interdisciplinary as it is today and the advent of gene editing tools, such as the CRISPR-Cas9 technology, and of optical approaches, such as genetically encoded calcium indicators and optical tweezers, now allow us to directly visualize and manipulate ciliary signalling in ways that were once inconceivable. These approaches will undoubtedly unlock our understanding of ciliary functions across the organism and developmental stages, ultimately highlighting new therapeutic targets to treat individuals with ciliopathies.

Girish Kale

A change in temperature is a common experience, evoking a natural curiosity about its effects on different biological processes. It has been known for a long time that temperature changes alter the rate of development, growth and regeneration in animals (Lillie and Knowlton, 1897). A plethora of studies have focused on effects of temperature in animals, and taken together they indicate, perhaps not so surprisingly, that temperature fluctuations distinctly impact different stages of the animal life cycle. For example, birth defects are strongly correlated with high fever during pregnancy in humans (reviewed by Edwards, 2006) without causing long-term effects in the parent. In other words, the same temperature regime is more detrimental to the embryo than it is to the adult. Moreover, embryos, unlike adults, have no way of escaping the temperature fluctuations through behavioural responses. Although these observations implicate temperature as a key factor determining the success rate of embryonic development, the developmental mechanisms underlying the response to temperature fluctuations remain relatively understudied.

Understanding the effect of temperature on embryo development is now more relevant than ever, given the global rise in temperatures and its impacts on biodiversity (https://www.ipcc.ch/sr15/). Climate change-related catastrophes are a common place occurrence, and it might be tempting to think that these would be the largest contributor to the impact of global warming on biodiversity. However, we also need to ask whether the rising temperatures can directly impact biodiversity due to the naturally greater susceptibility of embryo development. In the absence of behavioural responses, the embryo needs to rely on innate mechanisms to guard itself against the adverse effects of temperature spikes (reviewed by Irvine, 2020). As part of our recent work focusing on the effects of elevated temperature on fly embryo development (Kale et al., 2023 preprint), we analysed published datasets on genomic variations along continent-scale gradients of annual mean temperature (thermoclines) – thus assessing a ‘natural selection experiment’, where genes involved in adaptation to local temperature are expected to show allelic variation along the thermocline. Although one might expect, for example, genes related to the well-studied heat-shock response to vary in this manner, we did not observe this, but instead identified various proteins related to mitosis, signalling and metabolism as thermoclinal, implicating fine-tuning of cellular signalling as one mechanism of temperature adaptation.

It is likely that a 2-3°C rise in global average temperatures would correspond only to suboptimal, and not lethal, temperatures for most animals. Unfortunately, there is a great paucity of literature to help us imagine how embryonic development might fail at the brink of temperature optima: optima that have been established through adaptation to a climate that has been rather stable over millennia. Given the allelic variation in genes involved in cellular signalling processes, it is necessary to understand effects of elevated temperatures at the cell biological level, so that we can start to identify conserved principles that govern the cellular defects caused by elevated temperatures across all animals. To tackle this challenge, there is an urgent need to design research projects at the interface of cell biology, developmental biology, evolutionary biology and ecology. With research focusing on effect of elevated temperatures on embryonic development, we might have a chance to understand how biology responds to temperature changes. My hope is to understand how we might increase the robustness of embryo development to thermal fluctuations, especially in the context of conserving species on the edge of extinction.

Eirini Maniou

Morphogenesis (from the Greek μορϕογένεσης – ‘creation of form’) is the fundamental process through which an organism acquires its 3D shape. It requires the orchestrated behaviour of thousands of cells, collectively leading to large-scale tissue reorganisation and organ formation. The genetic and molecular control of morphogenesis has been studied across scales, from the miniscule Drosophila heart to the mammalian gut. This body of work has shown that spatial patterns of gene expression establish the timing and positioning of morphogenetic programmes, but gene expression alone cannot directly determine shape. To fill the gap, the field of biomechanics has gained significant momentum, with much research interest now shifted toward the role of mechanical forces and physical properties in the acquisition of embryonic shape.

Despite the hype, we are still in early days of understanding how molecular and mechanical signals influence each other in continuously changing tissues. For example, in neurulation, the interplay between morphogens (signalling molecules that regulate gene expression) and mechanical forces has just started to be explored. During neural tube closure, mechanical forces mediate the elevation and bending of the neural folds. In parallel, morphogen diffusion starts to pattern the neuroepithelium into progenitor domains. It was recently shown that in the mouse cranial neuroepithelium, Sonic hedgehog (Shh) controls a tissue-wide pattern of apical constriction, a cellular force-generating mechanism required to bring the neural folds together for neural fold elevation (Brooks et al., 2020). This suggests that morphogens can induce spatial patterns of both gene expression and mechanical properties, opening new avenues for our understanding of early development.

Apart from introducing spatial patterns, mechanochemical signals can also ensure pattern preservation during continuous morphogenesis (Fulton et al., 2022). This is nicely illustrated in zebrafish gastrulation, where graded cell motility downstream of Nodal signalling allows a subset of mesendoderm cells (leaders) to become fluid like and internalise at the blastopore lip. After their internalisation, the leader cells remain exposed to high Nodal signalling, which ensures cohesion and preserves mesendoderm patterning (Pinheiro et al., 2022).

But what comes first: mechanical changes, spatial rearrangement or cell fate specification? The temporal sequence of events is crucial, and although one might assume that genetically controlled cell fate determination would induce mechanical changes, the opposite is often the case. For example, in the preimplantation embryo, mechanical inputs precede blastomere sorting into inner and outer positions (Maitre et al., 2016). In the mouse morula, asymmetric inheritance of the apical domain generates blastomeres with different actomyosin contractility. This triggers the internalisation of blastomeres with higher contractility, leading to segregation of the inner cell mass from the trophectoderm. Contractile forces therefore act first and couple positioning and cell fate.

Key questions in the field are therefore how mechanical forces change in space and time, and to what extent they instruct cell fate specification. My work aims to answer these questions in the context of neural tube morphogenesis. To achieve this, we have been developing novel biomaterials to dynamically quantify and perturb mechanical forces in living vertebrate embryos (Maniou et al., 2024). Through multidisciplinary approaches, my aim is to use our understanding of neural tube closure mechanics to prevent neural tube defects. Given the rapid advancements in microscopy, genetic tools and computational power, now is a unique time to study biomechanics in embryo development. These technologies allow the unprecedented exploration of how mechanical forces shape development, with significant implications for understanding and preventing developmental disorders.

Louis Prahl

Traditionally reliant on in vivo experiments, the developmental biology field is increasingly embracing engineering principles to better understand how tissues and organs form. Our ability to manipulate stem cells and organoids has advanced hand-in-hand with developments in biomaterial scaffolds and microfluidic culture platforms. Synthetic signalling tools and biosensors permit real-time perturbation of developmental morphogens or recordings of developmental signals. Computational models can effectively integrate information across scales and accurately predict morphogenesis outcomes. As an engineer with broad interests in developmental biology, I have been fascinated with the use of engineering tools to guide tissue structure and decode the physical basis of morphogenesis.

Biomaterials have long held an important role in tissue engineering. Biologically derived materials (such as Matrigel) provide a trophic environment that supports growth and development, but their composition is ill-defined and can not be manipulated. Subsequent advances in hydrogel chemistry now afford tight control over scaffold properties (mechanics, ligand density, microstructure and degradability), effectively mimicking embryonic tissue properties for organoid culture (Xu et al., 2023). Moreover, researchers are now able to dynamically tune the properties or shape of these material scaffolds, allowing them to capture the spatiotemporal dynamics of developmental morphogenesis in a dish. Biocompatible materials also continue to find applications in traditional embryology questions. For example, the previous section discusses recent work by another PI fellow (Eirini Maniou), who developed a bioprinting approach that permits direct visualization of morphogenesis forces in intact embryos (Maniou et al., 2024).

Synthetic biology provides another important set of engineering tools to perturb and measure cell behaviour. Optogenetics – the control of cell signalling with light-sensitive fusion proteins – can be used to control signalling and provoke morphogenetic responses in multicellular tissues and embryos (Mumford et al., 2020). Because these tools are typically derived from endogenous signalling proteins, they can be used to isolate and study the effects of a particular signalling pathway on tissue form. For example, recent work from the Ebisuya laboratory created an optogenetic tool to stimulate apical constriction that enabled reproducible folding of cell monolayers and organoids (Martínez-Ara et al., 2022). Continued development and use of optogenetic tools at the tissue scale will allow us to guide cell movements, proliferation, signalling and differentiation towards building tissues with true-to-life structure and function, or to build novel tissue architectures. One exciting future prospect is using patterned light cues to guide the elaboration of repeating multicellular structures (such as branching kidney tubules) and to scale-up collecting duct networks in human kidney organoids (Shi et al., 2023).

Another long-standing part of the engineering toolkit well suited to provide deep insights into morphogenesis is computational modelling. Well-designed models should not only be able to explain biological phenomena in terms of physical principles, but also make testable predictions for future experiments. Alan Turing's work on pattern formation is an important historical example (Turing, 1952) and principles of his reaction-diffusion model are often used to predict biochemically driven patterning, such as epithelial branching (Menshykau et al., 2019). In my postdoctoral work, we used geometric and physical modelling to explore a developmental conflict between kidney tubule branching and limited organ surface area (Prahl et al., 2023). By drawing an analogy between kidney tubules and the physics of packed particles, we were not only able to relate anatomical rearrangements to mechanical forces, but also to predict new classifications of organizational defects and to relate those to published genetic mutants and our own experiments. Continuing to adapt and refine physics-based models will aid future efforts to study developmental processes in greater detail, reverse engineer conditions that cause congenital anomalies, and forward-engineer predictable organoid structures: advances to which I hope to contribute to in my own lab.

Keaton Schuster

The reasons why some animals can regenerate while others, such as humans, cannot is a fundamental question in regenerative biology. Epimorphic regeneration requires scarless wound healing, which in some species is followed by formation of a specialized zone of proliferating cells called a blastema. After this phase of regenerative growth, the cells contributing to the regenerate start to repattern and redifferentiate to the proper cell types so that function is restored. Animals tend to lose this regenerative capacity as they age (Yun, 2015). Regenerative biologists have made great strides in understanding the molecular mechanisms involved in blastema formation, proliferation, wound healing and pattern reformation, and what cellular changes occur to aging organs that eventually result in a loss of regenerative competence (Goldman and Poss, 2020; Yun, 2015). However, we do not understand how regenerative competence is acquired in the first place.

How does one develop regenerative capacity? This will likely depend on the cellular mechanism of regeneration. When regeneration is performed via resident pluripotent stem cells, such as neoblasts, the acquisition of regenerative capacity is associated with the timing of when these stem cells develop in the embryo. In the acoel Hofstenia miamia, neoblasts are derived from the 3a/3b blastomeres in the early embryo (Kimura et al., 2022). However, it is not known when during embryogenesis they obtain the ability to respond to injury. In planarians, piwi+ cells that will form neoblasts are established early in embryogenesis (Davies et al., 2017). However, regenerative capacity is acquired gradually from late in embryogenesis to early juvenile stages when polarity and differentiation of the major lineages is established, which suggests that there is a temporal delay between when the cells are specified and when they become competent to respond to injury (Booth et al., 2024 preprint).

Many regeneration-competent species and organ types do not regenerate via stem cells, but rather via cellular plasticity – where fully mature cell types undergo dedifferentiation and/or transdifferentiation to regenerate damaged tissue. This is commonly found in species such as fish and amphibians that can regenerate organs such as the heart or limbs, but cannot undergo whole body regeneration. In these species, our understanding of how cellular plasticity is specified is complicated by the fact that they undergo regulative development – meaning that they can compensate for ablated lineages – and can regenerate as embryos. This makes it difficult to identify the mechanisms that specify regenerative competence, and to delineate if and how they differ from developmental potential.

However, not all embryos undergo regulative development. Several species, including tunicates such as Ciona robusta (Conklin, 1905), the ctenophore Mnemiopsis leidyi (Martindale, 2016) and the annelid Capitella teleta (Boyd and Seaver, 2023), undergo mosaic development and are therefore regeneration incompetent during embryogenesis, but are regenerative as adults. Ciona, my experimental system of choice, can regenerate organs including the siphons (Whittaker, 1975), brain (Dahlberg et al., 2009) and heart (Schuster and Christiaen, 2023 preprint). We recently demonstrated that Ciona acquires cardiac regenerative competence late in metamorphosis, which positively correlates with maturation of the heart. The extensive molecular toolkit of Ciona and its close relationship to vertebrates position it as a unique and powerful model for understanding how cellular plasticity-based regenerative abilities are acquired during development. This will be one major focus of my future Origins of Regeneration Lab, where I will investigate the molecular mechanisms on how Ciona is able to acquire regenerative competence of its heart and other organs, such as the brain. This is a unique positive approach to regenerative biology in a field that often focuses on how we lose regenerative competence over developmental and evolutionary timescales. By focusing on how we obtain regenerative capacity in emerging model organisms, we hope to understand how regenerative competence can be bestowed to a regeneration-incompetent structure such as the human heart.

Clementine Villeneuve

How complex tissues and organs develop robustly and stereotypically during development despite stochastic fluctuations at molecular and cellular levels is a fascinating question that developmental biologists have been trying to solve for decades. This robustness relies on the spatio-temporal coordination of cell growth, specification and dynamic positioning. Secreted factors termed morphogens play a crucial role in choregraphing and coordinating spatial patterning, behaviour and morphologies of cell collectives, by controlling intracellular signalling, cytoskeletal rearrangements and gene transcription. Conversely, these changes in fate, morphology and behaviour lead to changes in morphogen secretion, diffusion and responsiveness, enabling fine-tuning of morphogenesis. Although the signalling cascades controlled by these morphogens have been extensively studied, the precise relationship between fate transitions, cell dynamics and positioning has yet to be elucidated.

Importantly, signalling outcomes depend not only on morphogen concentration but also on the frequency and duration of signalling, enabling a more robust encoding and transmission of biological information, and a greater signal diversity (Marshall, 1995; Dequéant et al. 2006; Uda et al., 2013; Selimkhanov et al., 2014). However, how these dynamics are decoded to induce specific cellular responses is still largely unknown. The development of new fluorescent molecular reporters combined with cutting-edge microscopy enables these elaborate signalling dynamics to be captured in space and time in living organisms and tissues. Understanding the interplay between signalling dynamics and fate specification is an exciting perspective, and we are just beginning to get a glimpse of the mechanisms involved.

Over the past few decades, it has been established that, while morphogens regulate cytoskeletal and adhesion complex organization, and thus cell mechanics, cell mechanics also feeds back to morphogen signalling by regulating how signals are decoded and propagated. Such mechano-chemical feedback loops are essential for the robust development of complex tissues and organs. In addition to their contribution to the formation of developing tissue through facilitating morphogenetic movements and generation of tissue structures, mechanical forces can also modulate cell fate. Emerging evidence suggests that morphogen production, transport and decay generate molecular noise that might be dampened by tissue architecture and mechanics, ensuring robust tissue patterning and morphogenesis. However, how single cells integrate biochemical and mechanical inputs to drive robust morphogenesis remains an open question in the field, one that I am excited to explore.

My system of choice, the developing hair follicle (HF), is an excellent paradigm for exploring the questions outlined here, as it beautifully recapitulates the developmental robustness involved in tissue patterning and morphogenesis, as well as requiring coordinated mesenchymal-epithelial crosstalk that involves both mechanical and chemical signal exchange. In mouse embryonic skin, precursor structures of the HF, epithelial thickenings termed placodes, arise from three consecutive waves producing morphologically identical, regularly interspersed HF placodes throughout the skin (Schmidt-Ullrich and Paus, 2005). Initial WNT-dependent HF pre-patterning emerges in the epithelium (Andl et al., 2002), generating a local source of FGF signals promoting underlying dermal condensation (Huh et al., 2013). We have recently shown that mechanical interactions between contractile mesenchymal cells and mechanically patterned epithelium then drive structural invagination and transcriptional specialization of the placode (Villeneuve et al., 2024). In parallel, on the tissue scale, signalling crosstalk between the epidermis and underlying dermis refines and reinforces HF patterning in a process proposed to resemble a Turing reaction-diffusion model (Sick et al., 2006). Given these precisely timed patterning events as well as the accessibility of the tissue to live imaging and manipulation, the skin is the ideal system with which to investigate the dynamic mechano-chemical feedback loops and the decoding of morphogen dynamics in the regulation of tissue morphogenesis.

I am looking forward to exploring these questions in an interdisciplinary approach at the interface between physics, chemistry and biology, and to integrating mechanobiology, developmental genetics, quantitative imaging and biophysical modelling to understand the complexity of morphogenesis. As cells communicate between different compartments, scientists also need to collaborate across several fields.

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