Embryonic neuro-development and associated childhood diseases
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.
Polarization, which confers asymmetry at molecular, cellular and tissue scales, is a fundamental process establishing key features of biological systems. In multicellular organisms, symmetry breaking triggers the specification of embryonic body axes, providing general landmarks for subsequent morphogenetic programs. Cells and tissues acquire complex morphological and functional polarity features, which, remarkably, are highly precisely positioned within the general body landmarks. This is the case of the developing nervous system, whose proper wiring requires multiple topographic controls. We investigate the topography of progenitor cell division, cell migration and axon navigation, with a focus on the developing spinal cord and peripheral ganglia derived from an embryonic population endowed with high proliferation and migration properties, the neural crest. In parallel, we investigate the pathogenic outcome of deregulations of these topography mechanisms. In particular, we study childhood malignancies with embryonic origin, such as the neuroblastoma, arising from the sympatho-adrenal neural crest, and the medulloblastoma arising from cerebellar progenitors . We exploit chick and mouse embryo animal models, combined with live imaging, cell and tissue cultures and large-scale transcriptomic approaches.
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..