Program

23/01/2023 – Pavel Tomancak (MPI-CBG, Dresden)

Evolution of Morphogenesis: the case of cephalic furrow 

I will discuss ideas and results on how we can understand evolution of morphogenesis through a comparative approach.

30/01/2023 – Kalika Prasad (IISER, Pune) 

Mechano-chemical feedbacks in plant regeneration   

Plants display remarkable developmental plasticity and can regenerate complete organ systems from a few existing cells in response to external inductive cues. A complete shoot system can be regenerated from undifferentiated callus through the age-old practice of de novo organogenesis. Recent studies have implicated a number of developmentally regulated genes in this process. While these studies provide a deterministic view, unitary principles associated with self-organisation of regenerating cells remain largely unknown. I will discuss how interplay between mechanical and biochemical effects sculpts the dome shaped meristem from regenerating progenitors in the absence of pre-patterning cues. 

06/02/2023 – Kyogo Kawaguchi  (Riken BDR, Kobe)

Topology and active matter physics in cultured nematic cells

Experiments in active matter physics naturally involve biological materials, ranging from molecular motors, bacteria, to mammalian cells. Here we use mouse neural progenitor cells, which are self-propelling bipolar-shaped cells with nematic interactions, to demonstrate how topological concepts can govern the collective dynamics in an active nematic system. We will first show how topological defects generated by the cells themselves make anomalous flow, which eventually leads to cell accumulation and dispersion. We will then describe how chiral edge flow arises in the stamp culture experiment and discuss how the mechanism is related to topological insulators. Lastly, we will describe our recent findings regarding the rules of cell motion and cell-to-cell interactions that lead to such patterning. These results show how ideas from statistical mechanics and topological condensed matter can be useful in understanding collective cell dynamics.

13/02/2023 – Eva Zaffarini (McCaig Institute, University of Calgary)

Cephalo-pelvic integration in hybrid mouse models and implications for human obstructed labour

The extremely tight fit between fetal head and maternal pelvic canal during childbirth is a cause of high mortality in humans. However, the relatively narrow size of the female pelvis, evolved for efficient bipedal locomotion, shows morphological covariation with head size, a highly heritable trait. This covariation is thought to reduce the risk of cephalo-pelvic mismatch and obstructed labour1. Morphological covariation arises through the evolution of mechanisms that mediate the coordinated development of functionally related characters2. Hybridization often reduces the degree of morphological integration between characters via genetic introgression3. My research investigates how hybridization in mice influences morphological covariation between skull and pelvis in relation to obstructed labour. After quantifying skull and pelvic shape in different wild mice species and their hybrids, I test the change in their degree and patterns of shape covariation, especially focusing on obstetric-relevant aspects of the pelvis and skull.

13/02/2023 – Maria Paraskevi Kotini (Biozentrum, University of Basel)

 Junctional Remodelling in Vascular Morphogenesis 

Blood vessel development is an early and crucial phenomenon associated with the growth and survival of a vertebrate embryo. Blood vessel morphogenesis is driven by coordinated endothelial cell behaviours, which depend on dynamic cell-cell interactions. In this context, remodelling of endothelial cell-cell junctions promotes morphogenetic cellular events while preserving vascular integrity. How these processes interact is poorly understood. To gain a better understanding on cell junction dynamics we use in vivo time-lapse imaging on transgenic zebrafish lines. This talk will focus on how endothelial cell junctions deal with an expanding lumen during early vascular development and how junctional remodelling contributes to the observed variation in blood vessel architectures in the developing organs. 

20/02/2023 –  Clare Buckley (PDN, University of Cambridge)

Building and Breaking the Neural Tube 

My lab investigates the morphogenesis of epithelial tubes during development and disease. Broadly, we want to know how epithelial tubes first polarise, how they open (rather than close) and why they break during disease. We are currently particularly interested in understanding the links between cell-cell adhesion, actomyosin contractility and cellular mechanics during secondary neurulation. To investigate these processes, we use high resolution imaging, CRISPR and optogenetics approaches in vivo, with the developing zebrafish neural tube and in vitro, within multicellular mouse embryonic stem cell cultures.

27/02/2023 – Agata Burian (University of Silesia, Katowice)

On the specification of leaf dorsiventrality 

Organogenesis in plants is closely related to the activity of the shoot apical meristem. The formation of lateral organs, such as leaves or flowers, is initiated at the meristem periphery by the establishment of local auxin maxima. In contrast to flowers, leaves are organs of dorsiventral symmetry, which is manifested in adaxial-abaxial leaf polarity. Adaxial and abaxial leaf sites are anatomically and functionally distinct, and their juxtaposition is essential for generating the flattened shape of a leaf blade. In this talk I will discuss how adaxial and abaxial cell fates are established at the shoot apical meristem of Arabidopsis, and what the role of auxin is in this process. Furthermore, I will show that that tracing cell lineages based on time-lapse imaging of a growing shoot apex is a useful toot that enables to link cell fates with dynamic gene expression patterns.

06/03/2023 – Lakshmi Balasubramaniam (Gurdon Institute, University of Cambridge)

Life and death of cells a mystery solved through biomechanics 

Tissue homeostasis of matured epithelia are maintained through a tight balance of cell proliferation and cell extrusion. The fate of the extruding cell and its viability plays a major role in determining health of the tissue. In this work we show that removal of E-cadherin an adherens junction protein leads to an increase in live cell extrusion. This live cell extrusion is accompanied by a switch in the direction of cell extrusion from apical to basal side. Mechanical measurements combined with phase field modelling show that local stress fluctuations regulate the mode of extrusions due to changes in cell-cell adhesions and internal activity. This form of live and basal extrusion can be a mode of cell extravasation during cancer. 

06/03/2023 – Guy Blanchard (PDN, University of Cambridge)

Tissue stress anisotropy and neighbour compression combine in mitosis to orient epithelial cell divisions 

The orientation of cell division (OCD) in the plane of epithelia drives tissue morphogenesis and relaxes stresses, with errors leading to pathologies. Cell elongation and local stress anisotropy have separately been shown to influence OCD, but it is unclear how interphase and mitotic cues interact to determine OCD.We tracked 730 dividing cells from interphase through cytokinesis in the planar polarised Drosophila embryonic ectoderm after gastrulation. The timing of known mitotic events relative to cytokinesis is remarkably consistent across cells, but planar OCD is highly variable.Using laser ablation, cell elongation as a proxy for local stress, and patterns of 3D cell shapes, we show that planar tissue-scale stress anisotropy switches orientation at the onset of the first cell divisions. OCD tracks this switch instantaneously, showing that prior interphase stress and cell elongation do not determine OCD in this tissue. Indeed, we show that compression from neighbouring dividing cells re-orients OCD only if compression occurs during metaphase. Thus, local stress anisotropy, resulting from a combination of tissue-scale stress anisotropy and local compression from neighbouring cells, orients cell elongation instantaneously during metaphase, which in turn directs OCD. However, we also find that the mitotic spindle at the end of metaphase, and hence the OCD, are consistently oriented away from the metaphase cell long axis and towards the anterior-posterior embryonic axis. This bias is very mild in elongated cells, stronger in more isotropic cells and its strength is predicted by the local strength of planar polarised junctional Myosin II.We conclude that in this Drosophila epithelium, mechanics, through local stress anisotropy, dominates OCD overall, but where cells are not strongly elongated Myosin II patterning takes over. 

13/03/2023 – Jesse Veenvliet (MPI-CBG, Dresden)

Connecting spaces and scales in stembryos 

Embryonic development requires multi-scale coordination of tissue morphogenesis, cellular behaviours, and gene expression to ensure highly reproducible differentiation outcome at the systems level. A deep understanding of the feedbacks that govern such robustness requires the study of the processes that pattern and shape the embryo in live specimens, in toto, across spatial and temporal scales. In mammalian embryogenesis, this remains a major challenge as the embryo develops in utero, precluding easy accessibility. These impediments can be overcome by coaxing pluripotent stem cells to form three-dimensional embryonic organoids (or stembryos) in vitro. Gastruloids are stembryos that break symmetry, elongate and self-organise the major body axes, but lack the stereotypical architecture of the embryo. We have shown that the latter can be unlocked by precisely timed addition of an extracellular matrix, resulting in trunk-like-structures (TLS) that molecularly and morphologically resemble the core part of the embryonic trunk. In contrast to its in vivo counterpart, these stembryos are easy to access, track, manipulate and scale. I will explain how we leverage these unique properties to identify minimal sets of inputs necessary to pattern and shape the mammalian embryo through controlled modulations of the system. Moreover, I will discuss novel frameworks we have developed that allow us to connect transcriptional, cellular and morpho-states in space and time, and how these help us to uncover the design principles of regulative development during critical windows of mammalian embryo morphogenesis.