the network on Developmental Biology at Sorbonne Université
The model organisms
Why model organisms?
Model organisms can be plants, microbes but are most often animals. They are used in scientific research to better understand biological processes and improve our knowledge of fundamental principles in biology as well as metabolism, health and disease in humans.
All living things share basic operating principles, therefore studying animals that are easily accessible can bring important findings for human health. They allow for performing experiments that would often be unethical to do with humans. Animals used as model organisms are animals with simplified systems. These organisms are often fast growing with a short generation time which provides the opportunity to carry out experiments over several generations. They can easily be manipulated and are cheap in rearing costs. Often they are easily genetically manipulated and offer the possibility of using mutants. These are organisms which have a change or mutation in their DNA which can give important information on a certain characteristic.
The conventional model organisms to study genetics are widely used throughout the network. These include for example chickens, mice (Mus musculus), zebrafish (Danio rerio), fruit fly (Drosophila melanogaster), yeast (Saccharomyces cerevisiae), the nematode worm (Caenorhabditis elegans) and the Western clawed frog (Xenopus tropicalis). Several species of fish, farmed or wild fish species representative of tropical, temperate and polar environments are being investigated as well. Not only economically important fish species are used in laboratory conditions, but certain mollusks (Haliotis tuberculata, Crassostrea gigas, Crassostrea rhizophorae, Sepia officinalis), annelids (Sabellaria alveolata), diatoms and corals (Acropora muricata, A. palmata, Porites lutea, P. astreoides) are gaining in importance.
One model organism often used in the André Picard Network is the ascidian or sea squirt. Ascidians are simple marine invertebrates that develop rapidly from an egg to a swimming tadpole, but unlike other invertebrate model organisms ascidians are in fact chordates and the closest extant relative of the vertebrates. They have a very simple morphology, a compact genome and they provide various options for molecular embryology and functional genomics.
Three species are currently being used under laboratory conditions
They are used for several research branches, for example unravelling the process of meiosis, fertilization and embryonic development. All cells respond to cues telling them when to divide, and in which direction. The temporal control of the cell cycle is achieved by a universally conserved core mechanism which is modified to the needs of specific cell types. The spatial control of cell division is also highly regulated. During meiosis two successive unequal cleavages create two tiny cells (polar bodies) and one large haploid egg. Errors in this process lead to aneuploidies, reduced fertility, and nonviable offspring. After fertilization, proper regulation of cell cycle duration and the orientation of cleavage planes dictate the number and size of cells, which governs the shape of the developing embryo and often the differentiation of tissue types (such as muscle, neurons, germ cells). Failure to coordinate temporal and spatial control of embryonic cell divisions leads to developmental pathologies and tumorigenesis. The eggs and embryos of ascidians are excellent model organisms for studying these cell cycle control mechanisms and their integration into the processes of meiosis, fertilization, and embryonic development.
Understanding the ability to regenerate organs and tissues is the long-term goal of research into stem cell biology and regenerative medicine. This is particularly interesting in light of the lack of conservation of regenerative capabilities during evolution: a salamander can regenerate an amputated limb but a human cannot. Colonial chordates provide experimentally accessible and reliable regenerative potential that can facilitate our understanding of the biology underlying regeneration. Colonial ascidians such as Botryllus schlosseri are the closest relatives to vertebrates that, beside embryogenesis, can adopt distinct developmental pathways (‘palleal budding’ or blastogenesis and ‘vascular budding’) to regenerate their entire body, including all somatic tissues and the germline.
Clytia hemispherica is a small jellyfish (5-20mm) present in all the world’s oceans. It has proved to be an excellent experimental model and is now routinely cultured and manipulated in the laboratory. Scientific interests have expanded to cover the zygotic as well as maternal phases of body axis patterning, as well as germ line/ stem cell biology. The genome is known and is used to address fundamental questions on the evolution of developmental patterning mechanisms
The first part of the Clytia lifecycles is a colony of polyps fixed on algae, rocks or sea shells. Certain polyps will specialize in reproduction, producing baby jellyfish by budding which join the plankton of the oceans until they settle down somewhere and form a new polyp colony. There are three parts in the life cycle: free swimming sexual medusa, planula larvae and polyp colonies. All stages can be conveniently maintained in the laboratory.
Embryos of the sea urchin (Paracentrotus lividus) embryo are used as a model for studies on checkpoint control during early stages of development.
Sea urchins are very well suited for laboratory studies, thanks to controllable spawning and external fertilization. The embryos are suitable for pharmacological treatments as well as for microinjection allowing the creation of transient transgenic animals and the specific functional knockdown or overexpression of targeted genes.
Chemosynthetic environments in the deep ocean, such as hydrothermal vents or oozing of oil as well as sunken wood or carcasses of large vertebrates are habitats difficult to access and characterized by very specific conditions.
Among the most original symbioses are those involving marine invertebrates and bacteria performing primary production based on the oxidation of reduced compounds. They are the foundation of the strong productivity observed around many hydrothermal vents, cold fluids sources and sunken organic substrates.
Because chemosynthetic symbioses appeared repeatedly during the evolution of bacteria and animals, we use comparative approaches and models in arthropods, molluscs and annelids.
Our tools range from the molecular biology microscopy (electronics and photonics) through isotopic analysis, and we perform some experiments in vivo through pressurized tanks.
Dispersal and colonization are generally done in the larval stage. But adults, especially Rimicaris exoculata, which should ensure supplies for its symbionts in chemicals, must be able to detect fluid emissions. We evaluate stress response capabilities and acclimatization of hydrothermal shrimps due to environmental variations, to assess their ability to withstand environmental perturbations, and their potential for resilience. We finally assess the role of the pressure in their thermal tolerance.
Several labs of the network use the amphioxus, a cephalochordate representing the earliest divergent lineage of chordates. It has kept all the morphological characteristics defining the chordate lineage (dorsal hollow nerve chord, dorsal notochord, pharyngeal gill slits) but remains an extremely simple organism, both anatomically and genomically.
The Xenacoelomorph worms, including Xenoturbella bocki and Paratomella rubra. These animals belong to the deuterostomes, but have vastly simplified morphologies compared to other extant members.
The Mamiellophyceae are unicellular marine green algae. These picoalgae serve as models for diverse research projects, ranging from their physiology to their evolutionary history, including their interactions with the environment, and their relationships with large DNA viruses.
The filamentous brown alga Ectocarpus siliculosus has been selected as a model because it possesses a small genome and exhibits a number of features that make it well adapted for genetic approaches.
Although a high percentage of marine organisms are being used for research, the most familiar terrestrial model organisms, as for example mice (Mus musculus) and Drosophila melanogaster, have their place within the network too.
As mentioned before, model organisms should be small animals, easy to rear, low maintenance costs, a relative short life cycle all of which is applicable when using mice under laboratory conditions. Yet this is not the reason why mice are so popular in biological and medical research. Mice are the most important mammalian model system due to the high percentage of similarities with humans, both genetically, immunologically as physiologically. They share about 95% of their genome with our own. Mice are most often used for genetic research because of the ease by which their genome can be manipulated. They have been very important for cancer research, diabetes and Alzheimer’s research.
The fruit fly Drosophila melanogaster is a recurrent model organism in genetic studies and developmental biology. They have been used for more than a century and were one of the first model organisms scientists used in their research. Since they are so small and have a very short generation time that they allow for large-scale experimental set ups over multiple generations. This is not always possible using other organisms due to practical and ethical reasons. Thanks to its long history a huge amount of data is readily available on the biology of this little animal. Their genetic composition shares a huge resemblance to its human counterpart, allowing for identifying new human genes using the knowledge of the fruit fly genome. The embryonic development of Drosophila has been thoroughly analyzed and has shed a light on important developmental processes and birth defects in humans.
(C) Magali Zbinden
Another way to understand the historical process of animal evolution is through computational techniques. These are used to study the genomes and protein structures, especially those of animals of a particular evolutionary significance.
Mathematical Modelling in Developmental Biology
The famous article by Alan Turing in 1952 "The chemical basis of morphogenesis” provided a first general explanation for the appearance of natural forms. This reaction-diffusion model allows explaining the appearance of 'patterns' on the skin of animals and is proposed as mechanism to achieve a segmentation during embryonic development. In the 1960s, L. Wolpert introduced the French Flag Model (FFM) assuming that a morphogen gradient allows for a more precise and realistic spatial location. These are the two general views that are currently being pursued by characterizing the location of the boundary between expressions of two different genes (Prochiantz A., Perthame B., C. Quininao and J. Touboul)
Other current work focuses on more specific areas. A collaboration between the laboratories of Developmental Biology, INRIA (Mycenae) and Jacques-Louis Lions Laboratory (Mathematics) focuses on processes of neurogenesis in the cerebral cortex in order to explain certain pathologies of the primary cilium, a sensory cell organelle. The mathematical multiscale model is confronted with experiments on mice overexpressing in the corresponding gene (F. Clement, Mr. Postel, S. Schneider-Maunoury, A. Karam).
Another example relates to the contraction of acto-myosin structures which plays a key role in the deformation of cells and tissue and which may be associated with movements over a mean curve. More generally this process is involved in morphogenesis and tissue repair of several organs (L. Almeida, A. Jacinto B. Ladoux).