Embryonic neuro-development and childhood cancers
Principal investigator: Valérie CASTELLANI
neuronal development | topographic signaling | axon guidance | cell division | cell migration | tumorigenesis metastasis
We investigate the development of the nervous system in the embryo and its deregulation in the context of pediatric cancers.
Our lab studies the interplays between cells and their environment during the formation of the nervous system. We seek to understand the mechanisms and molecular signals that allow progenitors and young neurons to locate themselves in space and to orient themselves correctly during the processes of migration and formation of neuronal circuits. These questions are mainly addressed through the study of a population of embryonic cells with remarkable properties, the neural crest. These are multipotent cells endowed with high migratory potential, that contribute to many tissues in the body. The neural crest is at the origin of nervous territories such as the sympathetic chain and the enteric nervous system, on which we are currently focusing our research. We are studying, for example, the developmental mechanisms that control the patterns of connections of the different populations of enteric neurons. In parallel, we study pediatric cancers of the nervous system in the light of their embryonic origin, in particular neuroblastoma, a cancer derived from the neural crest, and medulloblastoma from cerebellar progenitors. We seek to understand (i) what are the imprints of the embryonic context on the behavior of malignant cells, (ii) what phenotypic identities borrowed from the physiological lineages do these cells adopt to take advantage or highjack the developmental mechanisms and (iii) what are the characteristics shared between physiological lineages and tumoral cells and those specifically resulting from malignancy, which could make it possible to better target therapies on malignant cells while preserving healthy tissues. To model and thus be able to study thse childhood malignancies in an embryonic context, we have developed a paradigm of human tumor cell transplantation within selected tissues of the avian embryo. Our approaches combine experimental embryology and functional studies of genes of interest in our avian models, 3D light sheet microscopy to cartography cells and molecules at the whole embryo level, videomicroscopy, and large-scale transcriptomic analyses.
For the general public
How are being built our neuronal circuits? the newborn neuron develops an extension, the axon, destined to embark on an incredible journey, in search of the cells with which it will establish communication. Thus, during embryonic and post-natal development, millions of axons go in search of their partners, some remaining confined in the brain or the spinal cord, others colonizing the whole organism to innervate the muscles, the skin, viscera. Signals that allow axons to locate themselves in space, called topographic or guidance signals, are also used by cells that migrate to build nerve structures. Bringing each axon and each cell to its destination is a real challenge and it is these processes that our team is studying.
Can axons and cells get lost along the way or take wrong destination? Various childhood pathologies result in alterations in cell and axon navigation. Many have yet to be discovered, due to their early occurrence and consequent study difficulties. Moreover, this physiological phenomenon of migration also has a pathological correlate, that of pediatric cancers with an embryonic occurrence. Our team studies different contexts of pathology and also seeks to understand whether malignant cells use the topographic signals of embryogenesis in an opportunistic way, to disseminate and establish distant metastases.
26 February 2022
Post-doc Offer
Childhood malignancies of the nervous system: exploring the dissemination of tumoral cells in light of the mechanisms of the embryonic development.
The project aims at characterizing shared and unshared behaviors of malignant cells with their cells of origin labeled by specific fluorescent reporters, focusing on migratory processes. The objectives are to compare cell behaviors using imaging techniques and transcriptomic analyses to identify signaling pathways governing the pathfinding strategies of malignant cells during their dissemination.
See full offer description here..