Skip to content
What's on

Contemporary morphogenesis

Discussion meeting

Location

The Royal Society, London, 6-9 Carlton House Terrace, London, SW1Y 5AG

Overview

Scientific discussion meeting organised by Dr Kyra Anne Campbell, Dr Emily Noel, Dr Alexander Fletcher and Dr Natalia Bulgakova.

Zebrafish

Recent advances have revolutionised the field of Developmental Biology, heralding a new era of state-of-the art super-resolution live imaging, precision analyses, and à la carte genetic engineering. As a result, this fast-moving field now impacts on almost every other biological discipline. This meeting will showcase the cutting edge of research in Developmental Biology, with a focus on emerging talent.

Recorded audio of the presentations will be available on this page after the meeting has taken place. Meeting papers will be published in a future issue of Philosophical Transactions of the Royal Society B.

Call for posters

There will be a poster session at 16:20 on Monday 7 October 2019. If you would like to apply to present a poster please submit your proposed title, abstract (not more than 200 words and must be in third person), author list, name of the proposed presenter and institution to the Scientific Programmes team with the subject heading "Contemporary morphogenesis: poster abstract" no later than Monday 5 August 2019. Please note that places are limited and are selected at the scientific organisers' discretion. Poster/talk abstracts will only be considered if the presenter is registered to attend the meeting.

Whilst the posters are free to view for all registered participants, the corresponding optional drinks reception is ticketed. Drinks reception tickets can be purchased in advance during registration.

Attending this event

This meeting is intended for researchers in relevant fields.

  • Free to attend
  • Limited places, advance registration is essential
  • An optional lunch can be purchased during registration

Enquiries: contact the Scientific Programmes team

Event organisers

Select an organiser for more information

Schedule of talks

07 October

09:00-12:10

Session 1

8 talks Show detail Hide detail

Chairs

Dr Natalia Bulgakova, Bateson Centre, University of Sheffield, UK

09:05-09:30 Mechanisms of developmental morphogenesis in early embryos

Dr Bénédicte Sanson, University of Cambridge, UK

Show speakers

09:30-09:40 Discussion

09:45-10:15 Folding tissues across length scales: cell-based origami

Professor Adam Martin, Massachusetts Institute for Technology, USA

Abstract

Throughout the lifespan of an organism, tissues are remodeled to sculpt organs and organisms and to maintain tissue integrity and homeostasis. Apical constriction is a ubiquitous cell shape change of epithelial tissues that promotes epithelia folding and cell/tissue invagination in a variety of contexts. Apical constriction promotes tissue bending by changing the shape of constituent cells from a columnar-shape to a wedge-shape. Drosophila gastrulation is one of the classic examples of apical constriction, where cells constrict to fold the primitive epithelial sheet and internalize cells that will give rise to internal organs. Studies of Drosophila gastrulation have illustrated the intricate spatial and temporal organization of the proteins that drive apical constriction. Apical constriction of presumptive mesoderm cells occurs via repeated contractile pulses, specifically via the pulsed accumulation of myosin II motors. Contractile pulses are stabilised to promote incremental apical constriction, similar to a ratchet. Furthermore, the cytoskeleton exhibits clear spatial organization. The upstream signals that regulate myosin II activity exhibit are polarized to the center of the apical domain (medioapical). Actin turnover regulated by the microtubule cytoskeleton is important to maintain medioapical actomyosin connected to peripheral adherens junctions. Finally, apical actomyosin fibers connect between cells to form a supracellular cytoskeletal network. Intercellular connections in this cytoskeletal network are guided by tissue geometry and result in anisotropic tension that promotes a furrow shape. 

Show speakers

10:10-10:20 Discussion

10:20-10:50 Coffee

10:50-11:20 AP-DV embryo patterning synergy in cell shape change and tissue morphogenesis

Dr Matteo Rauzi, University Côte d'Azur, CNRS, France

Abstract

Morphogenesis is a process by which the embryo is reshaped into the final form of a developed animal. Tissue morphogenesis is under the control of genes which expression follows precise and instructive patterns that can extend from the anterior to the posterior (AP) or from the dorsal to the ventral (DV) axis of the embryo. While much work has been done in understanding how AP and DV patterning independently control morphogenesis, little is known on how cross-patterning functions.  We use the Drosophila embryo as a model system and focus on the process of tissue folding, process that is vital for the animal since folding defects can impair neurulation in vertebrates and gastrulation in all animals which are organized into the three germ layers. Past work has shown that an acto-myosin meshwork spanning the apical-medial side of prospective mesoderm cells and under the control of the embryo DV patterning plays a key role in mesoderm invagination. Nevertheless, experimental evidence and theoretical simulations have argued that apical constriction per se is not sufficient for invagination. In our lab we have uncovered a cell junctional lateral network under the control of both AP and DV patterning. This contractile network generates tension along the apical-basal axis and within the tissue plane 10-15 µm inside the mesoderm epithelium initiating lateral cell intercalation. Lateral forces in mesoderm cells seem to play a multivalent role both driving mesoderm extension and invagination. Finally, by implementing 4D multi-view light sheet imaging, infra-red femtosecond ablation to perturb the cytoskeleton and optogenetics to synthetically control tissue morphology, this work shines new light on the origin and functions of a novel mechanism responsible for simultaneous tissue elongation and folding.

Show speakers

11:20-11:30 Discussion

11:30-12:00 Epithelial cell reintegration: ins and outs

Dr Dan Bergstrahl, University of Rochester, USA

Abstract

Epithelial tissues form chemical and mechanical barriers in animal bodies, and must therefore maintain their integrity to function. This is a particular challenge during development, when new cells are being added to the tissue. Work in a number of systems shows that one answer to this challenge is cell reintegration: epithelial cells can be born protruding from the sheet, then reincorporate into it. The Bergstralh lab is working to understand this process. A previous study demonstrated that reintegration in the Drosophila follicular epithelium relies in part on Neuroglian (Nrg) a homophilic adhesion molecule that promotes axonal growth and pathfinding. Current research demonstrates that Nrg coordinates with another neuronal adhesion molecule, Fasciclin 3 (Fas3), and with the juxtamembrane spectrin-based cytoskeleton to drive reintegration. These proteins are likely to provide a traction force for the reintegrating cell, analogous to their function in the nervous system. Accumulating evidence suggests that this assembly is evolutionarily conserved, and also acts to maintain tissue integrity in proliferating vertebrate epithelia.

Show speakers

12:00-12:10 Discussion

12:10-13:10 Lunch

13:10-16:20

Session 2

9 talks Show detail Hide detail

Chairs

Dr Emily Noel, Bateson Centre, University of Sheffield, UK

13:10-13:40 Patterning morphogenesis through the planar cell polarity pathway

Dr Danelle Devenport, Princeton University, USA

Abstract

How cells assemble into precise spatial patterns from undifferentiated progenitors is a fundamental but still poorly understood question in developmental biology and tissue engineering. Using the mouse embryonic skin as a model system, which is decorated with regularly spaced, globally polarized hair follicles (HFs) that arise through self-organized epidermal-dermal signaling and planar polarized morphogenesis, the Devenport lab has established methods to perform long-term live imaging of epidermal development to capture the individual and collective cell behaviors that drive polarized morphogenesis of mammalian hair follicles. Using cell tracking methods to monitor the behaviors of every cell within developing hair placodes over the course of polarization, this live imaging approach revealed an unanticipated and novel pattern of collective cell movements that generates both morphological and cell fate asymmetry of developing follicles. The spatial patterning of hair follicle progenitors through Wnt and Shh pathways establish a morphogenetic program of collective cell motion. Moreover, this morphogenetic program displays unanticipated robustness, being able to withstand perturbations to spatial patterning though feedback between cell fate specification and cell motility.

Show speakers

13:40-13:50 Discussion

13:50-14:20 Revealing functional interactions between PAR proteins and the cytoskeleton in C. elegans zygote

Dr Josana Rodrigues, Newcastle University, UK

Abstract

C. elegans zygote polarity relies on the asymmetric distribution of key polarity effectors, the PAR proteins, which in turn drive the zygotes’ asymmetric cell division leading to the germline and somatic cell precursors. Zygote polarisation is triggered by the sperm-donated centrosome via two semi-redundant pathways. First, the centrosome reorganises the cortical acto-myosin meshwork, inducing a cortical flow away from the newly defined posterior pole. This flow transports a subset of PAR proteins to the anterior half of the zygote. Second, centrosomal-microtubules (MT) induce the membrane loading of another set of PAR proteins at the posterior. Anteriorly and posteriorly localised PARs mutually antagonise each other, further ensuring their asymmetric distribution. The existence of these two pathways confers robustness, but also makes it hard to tease these mechanisms apart and has impeded the identification of regulatory components for the MT pathway. We reasoned that knock-down of MT-pathway regulators in a mutant strain where the acto-myosin flow is perturbed, should lead to strong polarity defects and lethality that are not observed when knocked-down in a wild-type strain. Using this strategy we are identifying MT-pathway candidates and their characterisation is revealing new roles for microtubules in zygote polarity. I will discuss the unexpected role of a chromokinesin in cell polarity establishment.

Show speakers

14:20-14:30 Discussion

14:30-15:00 Tea

15:00-15:30 Left-right asymmetry of the heart : forming the right loop

Dr Sigolène Meilhac, Institut Imagine, Institut Pasteur, France

Abstract

Left-right partitioning of the heart underlies the double blood circulation. Impairment of left-right patterning leads to heterotaxy, including severe cardiac malformations. Asymmetric heart morphogenesis is initiated in the embryo, by the rightward looping of the cardiac tube, which determines cardiac chamber alignment. Whereas the molecular cascade breaking the symmetry has been well characterised, how Nodal signalling is sensed by precursor cells to generate asymmetric organogenesis remains unknown. Heart looping has been previously analysed simply as a direction. The associated 3D shape changes have now been reconstructed and quantified in the mouse. In combination with cell labelling and computer simulations, a model of heart looping has been proposed, centred on the buckling of the tube growing between fixed poles, which functions as a random asymmetry generator. Sequential and opposite left-right asymmetries have been identified at the poles, which bias the buckling, thus leading to a helical shape. Manipulating Nodal signalling in time and space shows that it is not involved in the buckling, but that it is required transiently in heart precursors, to amplify and coordinate asymmetries at the heart tube poles and thus generate a robust helical shape. Laterality defects are often partially penetrant, and thus it is a challenge to correlate embryonic anomalies with specific congenital defects. A multimodality imaging pipeline has been developed to phenotype laterality defects at multiple stages and at multiple scales within a single individual. These tools and model provide a novel framework to analyse the origin of complex congenital heart defects.

Show speakers

15:30-15:40 Discussion

15:40-16:10 Mechanics and mechanisms of tube formation

Dr Katja Röper, Medical Research Council Laboratory of Molecular Biology, UK

Abstract

We study the dynamic behaviour of epithelial sheets of cells during organ formation, in particular during the formation of tubular organs, using the formation of the tubes of the salivary glands in the Drosophila embryo as our main model system. These tubes form through a process of budding, and we have recently uncovered that cell behaviours across the tissue primordium, the placode, are highly patterned during the initial formation of the tube from a flat epithelial sheet. Within the apical domain, isotropic constriction near the invagination point combines with polarised cell intercalation away from the invagination point. In 3D, this was due to strong wedging of cells near the pit, as well as tilting towards it, and interleaving of cells across the tissue. I will discuss these findings in the light of the analysis of mutants that fail proper tube formation and that allow us to dissect the contribution of different behaviours as well as their potential mechanical interplay. We know that apical constriction in the placodal cells is driven by an apical medial acto-myosin network that depends on an intact longitudinal microtubule cytoskeleton. This microtubule network becomes acentrosomal concomitant with apical constriction, and we can now show that this change in organisation is driven by a two-pronged mechanism, combining loss of nucleation capacity at centrosomes with release of controsomal microtubules through severing followed by selective stabilisation of new free minus ends within the apical domain.

Show speakers

16:10-16:20 Discussion

16:20-18:15 Poster Session

08 October

09:00-12:10

Session 3

8 talks Show detail Hide detail

Chairs

Dr Kyra Campbell, Bateson Centre, University of Sheffield, UK

09:00-09:30 Cellular mechanisms of organ self-assembly in vivo

Professor Darren Gilmour, University of Zurich, Switzerland

Show speakers

09:30-09:40 Discussion

09:40-10:10 Dynamics of EMT and cell migration in Xenopus Neural Crest cells

Dr Eric Theveneau, Center for Integrative Biology, CNRS/Université Paul Sabatier, France

Abstract

Epithelial-mesenchymal transition (EMT) and cell migration are essential for numerous normal and pathological processes such as embryo development and cancer progression. Neural crest cells are multipotent embryonic stem cells whose EMT and migration rely on an array proto-oncogenes (e.g. Twist, Snail1/2, Ets1). In Xenopus, the early steps of neural crest development recapitulate what is observed in many carcinoma including an E-to-N cadherin switch followed by invasion of the local extracellular matrix. Neural crest cells express proteinases of the ADAM and MMP families and respond to factors that control tropism and homing of cancer cells such as CXCL12 and Semaphorins. Thus, Xenopus neural crest cells are an excellent model to study EMT and migration in a physiological context. Recently, Eric Theveneau’s group focused on two metalloproteinases (MMP14 and 28) that are known for their role in cancer invasion and wound healing, respectively. While most attention has been focused on the role of MMP14 and 28 in matrix remodeling during these processes, ongoing work on Xenopus neural crest cells by the Theveneau lab unraveled new functions for these enzymes, identifying them as early players during the EMT process and regulating the coordination between adjacent cell populations during morphogenesis.

Show speakers

10:10-10:20 Discussion

10:20-10:50 Coffee

10:50-11:20 Deciphering epithelial cell movements during embryogenesis

Professor Shankar Srinivas, University of Oxford, UK

Abstract

During early post-implantation embryogenesis of the mouse, the epiblast contributes the majority of the cells of the fetus but it is another tissue, the anterior visceral endoderm (AVE), that is responsible for imparting axial pattern upon the epiblast. AVE cells show a stereotypic unidirectional migration that is essential for correct orientation of the anterior-posterior axis. We do not understand how cells within epithelia such as the visceral endoderm show directed migration, how surrounding cells within intact epithelia accommodate the movement of a subset and the relative contributions of cell shape changes, regional differences in proliferation rates, oriented division etc. to such migration. Furthermore, we do not understand the extent to which movements within epithelia is coordinated with cell movements in abutting tissues such as the epiblast. To address these questions, we have used lightsheet microscopy to capture multi-dimensional image volumes of developing mouse embryos during AVE migration. To quantitatively analyse cell movements in the visceral endoderm, we have developed machine learning based approaches for the automated detection of cell boundaries and division events. I will discuss the new insights into cellular behaviour during AVE migration this approach reveals and a previously unknown movement within the epiblast that occurs in coordination with AVE migration.

Show speakers

11:20-11:30 Discussion

11:30-12:00 Signaling mechanisms that coordinate individual cell movements for epithelial migration

Dr Sally Horne-Badovinac, University of Chicago, USA

Abstract

The collective migration of cells within an epithelial sheet underlies tissue remodeling events associated with morphogenesis, wound repair, and the spread of many cancers. Yet little is known about how each cell coordinates its movements with those of its neighbors. Studying the rotational migration of the follicular epithelium in the Drosophila egg chamber, the Horne-Badovinac lab has identified two planar signaling systems that operate along leading-trailing cell-cell interfaces to coordinate individual cell movements for collective motility. In the first signaling system, the giant cadherin Fat2 localizes to the trailing edge of each cell and sends an attractive signal to the receptor tyrosine phosphatase Lar at the leading edge of the cell behind. In the second signaling system, the transmembrane semaphorin, Sema-5c, localizes to the leading edge of each cell and sends a repulsive signal to the Plexin A receptor at the trailing edge of the cell ahead. In this talk, Dr. Horne-Badovinac will introduce both signaling systems as well as her lab’s efforts to understand how these local signals are propagated to polarize the entire epithelium for directed migration.

Show speakers

12:00-12:10 Discussion

12:10-13:10 Lunch

13:10-17:00

Session 4

8 talks Show detail Hide detail

Chairs

Dr Alexander Fletcher, Bateson Centre, University of Sheffield, UK

13:10-13:40 Guts and gastrulation: the lineages & dynamics driving the morphogenesis of the gut endoderm in the mouse embryo

Dr Anna-Katerina Hadjantonakis, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center

Abstract

Gastrulation is a paradigm for the coupling of cell fate specification and tissue morphogenesis. In mammals, gastrulation transforms an embryo comprising two tissue layers (epiblast and visceral endoderm), into one comprising three tissue layers (epiblast, mesoderm and gut endoderm). The hallmark morphogenetic event of gastrulation is an epithelial-to-mesenchymal transition (EMT), which occurs at, and defines, a structure called the primitive streak. At the primitive streak epiblast cells lose pluripotency and undergo an EMT and begin to move away as they concomitantly acquire a mesoderm or definitive endoderm fate. Having left the vicinity of the primitive streak, cells specified as definitive endoderm will intercalate into the overlying visceral endoderm epithelium to generate the gut endoderm, the precursor tissue of the respiratory and digestive tracts and associated organs. Using various contemporary approaches, including imaging and transcriptomics, coupled with the analysis of mutants, we are systematically investigating the sequential steps leading to the formation of the gut endoderm, towards developing a mechanistic understanding of this process. I will highlight some open questions and overview some of our recent work.

Show speakers

13:40-13:50 Discussion

13:50-14:20 Coordination of patterning and growth in the spinal cord

Dr Anna Kicheva, Institute of Science and Technology (IST), Austria

Abstract

As the spinal cord grows during embryonic development, an elaborate pattern of molecularly distinct neuronal precursor cells forms along the DV axis. This pattern depends both on the dynamics of a morphogen-regulated gene regulatory network, and on tissue growth. We study how these processes are coordinated. Our data revealed that during mouse and chick development the gene expression pattern changes but does not scale with the overall tissue size. These changes in the pattern are sequentially controlled by distinct mechanisms. Initially, neural progenitors integrate signaling from opposing morphogen gradients to determine their identity by using a mechanism equivalent to maximum likelihood decoding. This strategy allows accurate assignment of position along the patterning axis and can account for the observed precision and shifts of pattern. During the subsequent developmental phase, cell-type specific regulation of differentiation rate, but not proliferation, elaborates the pattern. 

Show speakers

14:20-14:30 Discussion

14:30-15:00 Tea

15:00-15:30 Getting in shape: in vivo and in silico studies of tissue mechanics in growth control

Dr Yanlan Mao, University College London, UK

Abstract

Tissue folding is a fundamental process that shapes epithelia into complex 3D organs. The initial positioning of folds is the foundation for the emergence of correct tissue morphology. Mechanisms forming individual folds have been studied, but the precise positioning of folds in complex, multi-folded epithelia is less understood. In this talk, a novel computational model of morphogenesis will be presented. The model encompasses local differential growth and tissue mechanics, to investigate tissue fold positioning. The Drosophila wing disc is used as the model system, as there is spatial-temporal heterogeneity in its planar growth rates. This differential growth, especially at the early stages of development, is the main driver for fold positioning. Increased apical layer stiffness and confinement by the basement membrane drive fold formation, but influence positioning to a lesser degree. The model successfully predicts the in vivo morphology of overgrowth clones and wingless mutants via perturbations solely on planar differential growth in silico.

Show speakers

15:30-15:40 Discussion

15:40-17:00 Panel discussion/Overview (future directions)

Contemporary morphogenesis

7 - 8 October 2019

The Royal Society, London 6-9 Carlton House Terrace London SW1Y 5AG UK
Was this page useful?
Thank you for your feedback
Thank you for your feedback. Please help us improve this page by taking our short survey.