Project acronym COLOUR PATTERN
Project Morphogenesis and Molecular Regulation of Colour Patterning in Birds
Researcher (PI) Marie Celine Manceau
Host Institution (HI) COLLEGE DE FRANCE
Call Details Starting Grant (StG), LS3, ERC-2014-STG
Summary Animals display a tremendous diversity of patterns ‒from the colourful designs that adorn their body to repeated segmented appendages. Natural patterns result from the formation of discrete domains within developing tissues through the integration of positional cues by cells that consequently adopt specific fates and produce spatial heterogeneity. How can such developmental processes underlie the apparent complexity and diversity of natural patterns? We propose to address this long-standing question with an innovative experimental design: we will make use of natural variation as a powerful tool to facilitate the identification of patterning molecules and morphogenetic events. We will study colour pattern, a crucial adaptive trait that varies extensively in nature, from large colour domains to periodic designs. In amniotes, colour pattern is formed by spatial differences in the distribution of pigment cells and integumentary appendages. While the pigmentation system has been well characterized, the mechanisms governing the formation of compartments in the skin of wild animals have remained unclear, largely because laboratory models do not display ecologically-relevant colour patterns. We will use a combination of forward genetics, developmental biology, modelling, and imaging to study natural variation in the large colour domains of Estrildid finches and the periodic stripes of Galliform birds. For both phenotypes, we will characterize the organization of the embryonic skin and the mode of patterning (i.e., instructional patterning via external cues vs locally-occurring self-organization) underlying their formation, and identify the molecular factors and developmental processes contributing to their variation. Results from these studies will elucidate the biochemical events and tissue rearrangements orchestrating colour patterning in development and shed light on how these processes shape natural variation in this trait‒ and more generally, in natural patterns.
Summary
Animals display a tremendous diversity of patterns ‒from the colourful designs that adorn their body to repeated segmented appendages. Natural patterns result from the formation of discrete domains within developing tissues through the integration of positional cues by cells that consequently adopt specific fates and produce spatial heterogeneity. How can such developmental processes underlie the apparent complexity and diversity of natural patterns? We propose to address this long-standing question with an innovative experimental design: we will make use of natural variation as a powerful tool to facilitate the identification of patterning molecules and morphogenetic events. We will study colour pattern, a crucial adaptive trait that varies extensively in nature, from large colour domains to periodic designs. In amniotes, colour pattern is formed by spatial differences in the distribution of pigment cells and integumentary appendages. While the pigmentation system has been well characterized, the mechanisms governing the formation of compartments in the skin of wild animals have remained unclear, largely because laboratory models do not display ecologically-relevant colour patterns. We will use a combination of forward genetics, developmental biology, modelling, and imaging to study natural variation in the large colour domains of Estrildid finches and the periodic stripes of Galliform birds. For both phenotypes, we will characterize the organization of the embryonic skin and the mode of patterning (i.e., instructional patterning via external cues vs locally-occurring self-organization) underlying their formation, and identify the molecular factors and developmental processes contributing to their variation. Results from these studies will elucidate the biochemical events and tissue rearrangements orchestrating colour patterning in development and shed light on how these processes shape natural variation in this trait‒ and more generally, in natural patterns.
Max ERC Funding
1 483 144 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym EPAF
Project Role of Epithelial Apoptotic Force in Morphogenesis
Researcher (PI) Magali Aude Emmanuelle SUZANNE
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), LS3, ERC-2014-CoG
Summary Contrary to previous beliefs, recent studies have suggested that apoptotic cells play an important dynamic role during morphogenesis. Nonetheless, the mechanisms whereby dying cells drive tissue shape modification remain elusive.
Using the Drosophila developing leg as a model system to study apoptosis-dependent epithelium folding, we have recently shown that apoptotic cells produce a pulling force through the unexpected maintenance of their adherens junctions that serves as an anchor to an apico-basal Myosin II cable. The resulting apoptotic apico-basal force leads to a non-autonomous increase in tissue tension and apical constriction of surrounding cells, leading to epithelium folding. These results reveal that, far from being passively eliminated as generally thought, dying cells are very active until the end of the apoptotic process. The objective of the present proposal is to understand how apoptotic cells influence their surroundings from the micro-environment to the macro-scale level.
Our first aim is to dissect the cellular mechanisms governing the generation of the apoptotic force and its transmission to the tissue, both apically through planar polarity and basally through the extra-cellular matrix (ECM), in parallel with the identification of the network of genes orchestrating apoptosis-dependent morphogenesis through a powerful genetic screen. Interesting preliminary results have already identified the epithelio-mesenchymal-transition gene Snail as essential for the progression of apoptosis, thus validating our approach.
Therefore, the second aim of this project is to compare Snail function in the control of adhesion and ECM dynamics and in the generation of tissue tension in both EMT and apoptosis. This original comparative study should bring novel insight into these two fundamental processes.
To perform this work, we will use elegant genetic tools combined to state-of-the-art live imaging techniques, together with robust biophysical modelling.
Summary
Contrary to previous beliefs, recent studies have suggested that apoptotic cells play an important dynamic role during morphogenesis. Nonetheless, the mechanisms whereby dying cells drive tissue shape modification remain elusive.
Using the Drosophila developing leg as a model system to study apoptosis-dependent epithelium folding, we have recently shown that apoptotic cells produce a pulling force through the unexpected maintenance of their adherens junctions that serves as an anchor to an apico-basal Myosin II cable. The resulting apoptotic apico-basal force leads to a non-autonomous increase in tissue tension and apical constriction of surrounding cells, leading to epithelium folding. These results reveal that, far from being passively eliminated as generally thought, dying cells are very active until the end of the apoptotic process. The objective of the present proposal is to understand how apoptotic cells influence their surroundings from the micro-environment to the macro-scale level.
Our first aim is to dissect the cellular mechanisms governing the generation of the apoptotic force and its transmission to the tissue, both apically through planar polarity and basally through the extra-cellular matrix (ECM), in parallel with the identification of the network of genes orchestrating apoptosis-dependent morphogenesis through a powerful genetic screen. Interesting preliminary results have already identified the epithelio-mesenchymal-transition gene Snail as essential for the progression of apoptosis, thus validating our approach.
Therefore, the second aim of this project is to compare Snail function in the control of adhesion and ECM dynamics and in the generation of tissue tension in both EMT and apoptosis. This original comparative study should bring novel insight into these two fundamental processes.
To perform this work, we will use elegant genetic tools combined to state-of-the-art live imaging techniques, together with robust biophysical modelling.
Max ERC Funding
2 311 844 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym LUPINROOTS
Project Unravelling cluster root development in white lupin
Researcher (PI) Benjamin Peret
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS3, ERC-2014-STG
Summary Plant development is continuous throughout their lifetime and reflects their ability to adapt to their environment. This developmental plasticity is very obvious in the development of the root system. Surprisingly, the fundamental mechanisms of root development have been studied into great detail but the effect of the environment on its plasticity is still largely unknown. I will use phosphate, since this nutrient has a very low mobility in soil, as a mean to study plant developmental adaptation in white lupin.
This species has developed extreme adaptive mechanism to improve phosphate uptake by producing structures called “cluster roots”. They are dense clusters of lateral roots with determinate development and highly specific physiology. I will develop new tools to identify cluster root mutants in white lupin, sequence white lupin genome, perform tissues specific transcriptomics and perform full molecular characterization of selected genes. This project will also lead me to compare adaptive mechanisms between white lupin and narrow-leafed lupin, a closely related species that does not produce cluster roots. We will also test whether it is possible to transfer the ability to form cluster roots in this species. Altogether, this project will lead to a major advance in our capacity to understand how plants are able to sense and respond to their environment and how evolution has selected adaptive developmental mechanisms to improve their capacity to use limited resources.
This project focuses on the most extreme developmental adaptation produced in response to phosphate starvation. It is ambitious, as it will necessitate the development of several tools. However, it is highly feasible since it builds on my previous experience and important outcome can be expected in term of crop improvement and means to reduce the use of phosphate fertilizers.
Summary
Plant development is continuous throughout their lifetime and reflects their ability to adapt to their environment. This developmental plasticity is very obvious in the development of the root system. Surprisingly, the fundamental mechanisms of root development have been studied into great detail but the effect of the environment on its plasticity is still largely unknown. I will use phosphate, since this nutrient has a very low mobility in soil, as a mean to study plant developmental adaptation in white lupin.
This species has developed extreme adaptive mechanism to improve phosphate uptake by producing structures called “cluster roots”. They are dense clusters of lateral roots with determinate development and highly specific physiology. I will develop new tools to identify cluster root mutants in white lupin, sequence white lupin genome, perform tissues specific transcriptomics and perform full molecular characterization of selected genes. This project will also lead me to compare adaptive mechanisms between white lupin and narrow-leafed lupin, a closely related species that does not produce cluster roots. We will also test whether it is possible to transfer the ability to form cluster roots in this species. Altogether, this project will lead to a major advance in our capacity to understand how plants are able to sense and respond to their environment and how evolution has selected adaptive developmental mechanisms to improve their capacity to use limited resources.
This project focuses on the most extreme developmental adaptation produced in response to phosphate starvation. It is ambitious, as it will necessitate the development of several tools. However, it is highly feasible since it builds on my previous experience and important outcome can be expected in term of crop improvement and means to reduce the use of phosphate fertilizers.
Max ERC Funding
1 997 103 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym PlastiCell
Project Using a natural cellular plasticity event to decypher the cellular requirements and molecular circuitry promoting transdifferentiation at the single cell level.
Researcher (PI) Sophie Jarriault
Host Institution (HI) CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE
Call Details Consolidator Grant (CoG), LS3, ERC-2014-CoG
Summary How differentiated cells can change their identity is a fascinating question. Indeed, natural interconversions between functionally distinct somatic cell types (aka transdifferentiation, Td) have been reported in species as diverse as jellyfish and mice, while experimentally induced reprogramming of differentiated cells has been demonstrated. The relative ease with which cellular identities can be reprogrammed raises a number of exciting questions: What mechanisms and steps allow a given cell, but not its apparently identical neighbours, to naturally acquire a new plasticity potential and change its identity? How does the cellular context influence the ability of a cell to be reprogrammed? What cellular mechanisms must be counteracted to allow natural reprograming to occur? What circuitry underlie the impressive efficiency observed in natural events? The proposed project tackles these questions:
To systematically identify the molecular networks and cellular requirements of Td, we established a simple model of natural Td, in C. elegans, where the conversion of a rectal cell into a motoneuron is followed in vivo. This model is unique: it is 100% efficient, predictable and provides the first unambiguous demonstration, at the single cell level, of natural Td. The study of such natural event has revealed a key asset to unravel the discrete steps of the process, their control and the conserved cell plasticity factors promoting its initiation, while leading to important concepts conserved across phyla.
We propose here 4 aims to push new frontiers and: i) Define what makes a cellular context permissive; ii) Elucidate the conserved nuclear complexes and network architecture promoting efficient reprogramming; iii) Identify mechanisms that protect the differentiated identity and act as a brake to Td. Understanding cell plasticity in vivo will have a tremendous impact on our perception of developmental and cancerous processes and could open new avenues for regenerative medicine.
Summary
How differentiated cells can change their identity is a fascinating question. Indeed, natural interconversions between functionally distinct somatic cell types (aka transdifferentiation, Td) have been reported in species as diverse as jellyfish and mice, while experimentally induced reprogramming of differentiated cells has been demonstrated. The relative ease with which cellular identities can be reprogrammed raises a number of exciting questions: What mechanisms and steps allow a given cell, but not its apparently identical neighbours, to naturally acquire a new plasticity potential and change its identity? How does the cellular context influence the ability of a cell to be reprogrammed? What cellular mechanisms must be counteracted to allow natural reprograming to occur? What circuitry underlie the impressive efficiency observed in natural events? The proposed project tackles these questions:
To systematically identify the molecular networks and cellular requirements of Td, we established a simple model of natural Td, in C. elegans, where the conversion of a rectal cell into a motoneuron is followed in vivo. This model is unique: it is 100% efficient, predictable and provides the first unambiguous demonstration, at the single cell level, of natural Td. The study of such natural event has revealed a key asset to unravel the discrete steps of the process, their control and the conserved cell plasticity factors promoting its initiation, while leading to important concepts conserved across phyla.
We propose here 4 aims to push new frontiers and: i) Define what makes a cellular context permissive; ii) Elucidate the conserved nuclear complexes and network architecture promoting efficient reprogramming; iii) Identify mechanisms that protect the differentiated identity and act as a brake to Td. Understanding cell plasticity in vivo will have a tremendous impact on our perception of developmental and cancerous processes and could open new avenues for regenerative medicine.
Max ERC Funding
2 000 000 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym SegregActin
Project Building Distinct Actin Filament Networks in a Common Cytoplasm
Researcher (PI) Alphee Michelot
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS3, ERC-2014-STG
Summary "The ability of cells to use the actin cytoskeleton for a diversity of cellular processes is due to the fact that actin filaments, although assembled from identical subunits, are organized in a wide variety of structures of appropriate geometrical, dynamical and rheological properties. Key players in this regulation are specific sets of actin binding proteins (ABPs) interacting with each actin networks, to modulate spatially and temporally their properties.
With this project, I want to understand 1/ how cells can generate the formation of actin structures of appropriate ABP composition from a common pool of cytoplasmic components and 2/ the relationship between the ABP composition of an actin network, its geometrical and dynamical properties, and its response to mechanical deformations.
I will hypothesize that the generation of an actin network of appropriate ABP composition can be explained with an original model, taking into account the facts that 1/ actin filaments in cells are not all structurally identical, but adopt specific conformations that are favored and stabilized by certain families of ABPs; and 2/ the interaction of ABPs with actin depends of the geometrical organization of the filaments.
Because this project imposes to study protein-protein interactions in the presence of multiple partners, I propose to develop an unprecedented strategy combining 1/ "bottom-up" reconstitutions, where limited sets of ABPs are added one-by-one in the system to understand their combined activities with actin; and 2/ "top-down" reconstitutions with protein extracts prepared from a genetically-tractable organism (the yeast S. cerevisiae), where proteins can be removed one-by-one, in order to study actin network properties in near-physiological conditions.
This project will shed a new light on how cells organize their interior, and will represent a unique opportunity to understand how modifications in the expression of ABPs are associated with actin network defects."
Summary
"The ability of cells to use the actin cytoskeleton for a diversity of cellular processes is due to the fact that actin filaments, although assembled from identical subunits, are organized in a wide variety of structures of appropriate geometrical, dynamical and rheological properties. Key players in this regulation are specific sets of actin binding proteins (ABPs) interacting with each actin networks, to modulate spatially and temporally their properties.
With this project, I want to understand 1/ how cells can generate the formation of actin structures of appropriate ABP composition from a common pool of cytoplasmic components and 2/ the relationship between the ABP composition of an actin network, its geometrical and dynamical properties, and its response to mechanical deformations.
I will hypothesize that the generation of an actin network of appropriate ABP composition can be explained with an original model, taking into account the facts that 1/ actin filaments in cells are not all structurally identical, but adopt specific conformations that are favored and stabilized by certain families of ABPs; and 2/ the interaction of ABPs with actin depends of the geometrical organization of the filaments.
Because this project imposes to study protein-protein interactions in the presence of multiple partners, I propose to develop an unprecedented strategy combining 1/ "bottom-up" reconstitutions, where limited sets of ABPs are added one-by-one in the system to understand their combined activities with actin; and 2/ "top-down" reconstitutions with protein extracts prepared from a genetically-tractable organism (the yeast S. cerevisiae), where proteins can be removed one-by-one, in order to study actin network properties in near-physiological conditions.
This project will shed a new light on how cells organize their interior, and will represent a unique opportunity to understand how modifications in the expression of ABPs are associated with actin network defects."
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
