Program

10/10/2022 – Giulia Paci (LMBC, University College London)

Title TBC

17/10/22 – Mauricio Rocha Martins (Instituto Gulbenkian Ciência, Portugal) 

How tissues orchestrate growth and morphogenesis – lessons from the vertebrate retina  

Most developing tissues acquire functional architecture as they still

undergo significant growth. How differentiating and proliferating cells cooperate in crowded yet dynamic tissue environments in order to prevent spatial interference remains, however, largely unclear. In this seminar, I will introduce how we use the developing retina of zebrafish and human organoids to probe cell movements important for tissue growth and organization, as well as their coordination in space and time. I will present how quantitative imaging approaches revealed an unknown bidirectional migration phenomenon of one of the most studied retinal neurons, photoreceptors. Interestingly, this bidirectional migration occurs at peak proliferation stages and culminates in a transient relocation of the entire cell population away from the proliferative zone. We performed a comprehensive analysis of the molecular motors driving photoreceptor movements in different directions, and then exploited these mechanistic insights to determine the relevance of their movements to overall tissue morphogenesis. We found that photoreceptor movements are not directly needed for their correct lamination. However, blockage of photoreceptor migration congests the mitotic zone of the tissue causing intense progenitor delamination followed by secondary tissue disorganization. Our findings highlight that neuronal migration can play an important role in coordinating growth and morphogenesis by preventing spatial competition. 

17/10/22 – Robin Beaven (University of Edinburgh) 

Multi-organ FGF crosstalk orchestrates the construction of the water conserving cryptonephridial complex in a beetle

Tenebrionid beetles can survive in arid environments, and a key feature underlying their ability to conserve water is the cryptonephridial complex (CNC). It recovers water from the rectal contents and recycles it back to the body. The complex arises from a radical reorganisation of the insect body plan. It comprises two organs found in most insects, the hindgut and renal/Malpighian tubules, which come to lie in counter current arrangement. The renal tubules generate a high ionic concentration to draw water out of the hindgut and return it to the body. It is surrounded by an insulating layer of tissue, the perinephric membrane, which appears to be unique to insect CNCs. In the Denholm lab we are studying how this organ system develops, including how differentiation of the specialised cells within it is controlled. Here I will talk about the mechanisms by which the distinct tissues generating the CNC are assembled during development. Using Tribolium, we find that sequential crosstalk between the hindgut, renal tubules and perinephric membrane precursor cells, involving multiple Fibroblast Growth Factor (FGF) ligands and receptor isoforms, establishes the counter current configuration and close apposition of the rectum with renal tubules, as well as the recruitment of the perinephric membrane. We also identify that the perinephric membrane develops from a distinct population of mesodermal cells not previously described. This provides an elegant example of FGF signalling orchestrating elaborate morphogenic interactions between three tissues, to generate one of the most powerful water conservation systems in nature. 

24/10/2022 – Jody Rosenblatt (King’s College London)

Cell extrusion—an exciting start to the end of life 

31/10/2022 – Bénédicte Charrier (Station Biologique de Roscoff, Sorbonne University)

Submerged by 4-way junctions: how the early embryo of the brown alga Saccharina e-copes 

Saccharina is a brown marine alga (kelp) that develops a pear-shaped monolayered cell sheet during embryogenesis. Notably, this shape is maintained throughout embryogenesis and, within the sheet, the cells are cuboids arranged in a grid, resulting in the so-called 4-way junctions pattern. Interestingly, this tissue pattern has been described as rare and unstable in land plants (Thompson, 1942; Lloyd, 1991) whereas it is commonly observed in kelp embryos  (Sauvageau, 1918). 

Using a 2D-vertex mechanical model, we have studied the cellular parameters that underlie the formation of this grid during growth, while maintaining the initial shape of the embryo. I will show the extent to which Saccharina must control these parameters, especially under stochastic conditions aimed to reflect real-life fluctuations in cell turgor and in cell division time, position and orientation. In particular, I will assess the extent to which this model can account for the diversity of shapes observed in living algal embryos. 

 

07/11/2022 –  Dagmar Iber (ETH Zurich)

Computational Models of the Development of the Central Nervous System 

 
The central nervous system develops from the neural plate, which folds into the neural tube. Subsequently, morphogen gradients define distinct neural progenitor domains along the dorsal-ventral axis, which give rise to the central nervous system. In my talk, I will present recent work from the group that addressed the folding mechanism of the neural tube [1], and that showed that the gradient-based patterning is much more precise than previously thought [2]. With the help of cell-based modelling, we further found that high patterning precision requires small cell diameters, pointing to the long-elusive evolutionary driving force behind the emergence of pseudostratified epithelia [3,4]. Finally, I will discuss the biophysical constraints that define the complex shape of cells in pseudostratified epithelia [5-8], and present our recently developed 3D simulation framework for the data-driven simulation of epithelial cell dynamics. 

14/11/2022 – Shankar Srinivas (DPAG, University of Oxford)

Single-cell phenomics reveals behavioural and mechanical heterogeneities underpinning migratory activity during mouse anterior patterning  

AVE cells show a stereotypic unidirectional migration essential for correct orientation of the anterior-posterior axis. They migrate within a simple epithelium, but it is unknown how they negotiate their way amongst the surrounding Visceral Endoderm (VE) cells while it remains a monolayer and retains epithelial integrity. It is unclear what the relative contributions of cell shape changes, regional differences in proliferation rates, oriented division etc. are to such migration. To address these questions, we used lightsheet microscopy to generate a multi-embryo, single-cell resolution, longitudinal dataset of cell behaviour. We developed a machine learning based computational pipeline to segment cells and extract morphological and behavioural parameters of AVE and surrounding VE cells. Unbiased clustering of this single-cell ‘phenomic’ dataset reveals considerable patterned phenotypic heterogeneity within the VE and AVE and a previously unknown behavioural sub-grouping within the AVE. It reveals that while migrating, AVE cells remain relatively constant in morphology, do not exchange neighbours and appear crowded, with a constant relatively low apical surface area. In contrast, VE cells ahead of them become highly elongated, undergo neighbour exchange and show bilateral polonaise-like rotational movements. The dataset shows that AVE cells are also characterised by higher levels of apical and junctional F-actin, suggesting they may be mechanical distinct from surrounding VE cells, which we verify in mouse embryos using a live tension sensor probe and Fluorescence Lifetime imaging. These data lead us to propose a model whereby AVE migration is facilitated by an unjamming transition of surrounding VE cells, while AVE cells themselves remain in a jammed state throughout migration. 

21/11/2022 – Lucie Riglet (Sainsbury Laboratory, Cambridge University )

Understanding how flowering plants build communication devices on their petals 

The colourful patterns on the corolla of flowering plants are key signals to attract pollinators, contributing to plant reproductive success and diversification. Hibiscus trionum flowers display a striking bullseye pattern on their petal, emerging from the combination of a basal purple spot made of flat, elongated, striated cells, with a white distal region of conical and smooth cells. Both regions are separated by a boundary positioned at 1/3rd from the petal base. How is this boundary specified during development and how its position can vary during evolution to change pattern proportions is not understood. 

We developed a quantitative imaging pipeline to start deciphering the mechanisms that specify the distinct regions of the bullseye in developing petals. Using this pipeline, we captured early cellular behaviour in H. trionum petal epidermis and showed that growth and division are not uniform and follow a pre-pattern long before any sign of the bullseye become visible. To probe the mechanisms accounting for a change in bullseye dimensions, we characterised natural variants/transgenic lines that differ in bullseye size and tested whether bumblebees can distinguish and/or prefer specific proportions. 

21/11/2022 – Katharine Goodwin (Princeton, MRC LMB)

Branching morphogenesis of the lung: tales of the sculptor and the sculpture

Branching morphogenesis transforms simple tubes of cells into vast, tree-like networks essential for organ function. In the embryonic mouse lung, smooth muscle differentiation around the airway epithelium physically shapes emerging branches. Here, we delved into the behavior of the sculptor itself, airway smooth muscle, and examined how it influences cell fate patterns within the underlying sculpture, the airway epithelial tree. Using genetic perturbations and single-cell bioinformatics, we demonstrate phenotypic plasticity in airway smooth muscle that ensures robust branching morphogenesis. Then, using genetic and mechanical perturbations of epithelial fate and form, we show that patterns of epithelial cell fate depend on the physical signals imposed by branching morphogenesis and airway smooth muscle wrapping.

28/11/2022 – Ewa Paluch (PDN Department, Cambridge University)

Dynamics and mechanics of cell shape changes during cellular state changes 

A precise control of cell morphology is key for cell physiology, and cell shape deregulation is at the heart of many pathological disorders, including cancer. Furthermore, transitions between cellular states are often associated with changes in cell shape, and strong evidence points to the existence of feedbacks between mechanics, morphology and cell state. 
Cell morphology is intrinsically controlled by mechanical forces acting on the cell surface. In animal cells, cell surface mechanics are primarily determined by the cellular cortex, a thin network of actin filaments and myosin motors underlying the plasma membrane. We investigate how the mechanical properties of the cell surface arise from the microscopic organisation of the cortex, and how changes in these properties drive cell deformation. We also investigate cell shape dynamics when cells transition between different cellular states, such as during differentiation, cell division, or EMT. Using a combination of cell biology experiments, quantitative imaging and physical modelling, we aim to understand the control of cell shape across scales. 

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