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..

Start Up

image001-2-260x53Oncofactory is a start-up founded in 2016 as a spin-off of the Castellani lab, based on the work of Dr. Céline Delloye Bourgeois and Dr. Valérie Castellani at the NeuroMyoGene Institute in Lyon. Oncofactory offers an innovative in vivo platform suited for all cancers consisting in the creation of miniaturized replicas of patient tumors in an embryonic organism. Tumors are analyzed in the whole organism using 3D microscopy. Replicas can be collected back for a range of large scale molecular analysis. Using its unique technological platform Oncofactory evaluates the efficacy, studies the mechanisms of action of therapeutic candidates, helps the design of combi-therapies through a dedicated program combining transcriptomic analysis and its model of patient tumors replicas.

REACT4KIDS

REACT4Kids Notre équipe appartient au réseau REACT4KIDS (REsearchers in oncology ACTing for kids), un réseau collaboratif de recherche fondamentale en oncologie pédiatrique, dont les missions sont de favoriser les échanges entre les acteurs de ce secteur et de répondre à des problématiques communes. REACT4KIDS a un seul objectif: permettre de mieux comprendre les bases moléculaires des cancers des enfants et adolescents, afin de pouvoir dans l’avenir mieux les soigner.


Team Members

  • Valérie CASTELLANIResearcher CNRS, HDR – valerie.castellani@univ-lyon1.fr
  • Céline DELLOYE-BOURGEOISResearcher, CNRS – celine.delloye-bourgeois@univ-lyon1.fr
  • Servane TAUSZIG-DELAMASUREResearcher, CNRS, HDR – servane.tauszig-delamasure@univ-lyon1.fr
  • Julien FALKResearcher, CNRS, HDR – julien.falk@univ-lyon1.fr
  • Frédéric MORETAssistant Professor, UCBL, HDR – frederic.moret@univ-lyon1.fr
  • Muriel BOZONResearch Assistant, CNRS – muriel.bozon@univ-lyon1.fr
  • Emy THEOULEResearch Assistant, UCBL – emy.theoulle@univ-lyon1.fr
  • Karine THOINETResearch Assistant, CNRS – karine.thoinet@univ-lyon1.fr
  • Florie REYNAUDResearch Assistant, UCBL – florie.reynaud@univ-lyon1.fr
  • Caroline IMBERTResearch Assistant, UCBL – caroline.imbert@univ-lyon1.fr
  • Franck BOISMOREAUPost-doc, UCBL – franck.boismoreau@univ-lyon1.fr
  • Sophie CALVETPost-doc, UCBL – sophie.calvet@univ-lyon1.fr
  • Maëlys ANDREPhD student, UCBL – maelys.andre@univ-lyon1.fr
  • Benjamin VILLALARDPhD student, CNRS – benjamin.villalard@univ-lyon1.fr
  • Marion MALLETM2
  • Raphael GURYM2
  • Sofia DJAMAIM1
  • Laurine FIGEACM1

Selected publications

  1. An avian embryo patient-derived xenograft model for preclinical studies of human breast cancers.
    Jarrosson L, Costechareyre C, Gallix F, Ciré S, Gay F, Imbaud O, Teinturier R, Marangoni E, Aguéra K, Delloye-Bourgeois C, Castellani V.
    iScience (2021) — Show abstract
  2. X-linked partial corpus callosum agenesis with mild intellectual disability: identification of a novel L1CAM pathogenic variant.
    Bousquet I, Bozon M, Castellani V, Touraine R, Piton A, Gérard B, Guibaud L, Sanlaville D, Edery P, Saugier-Veber P, Putoux A.
    Neurogenetics (2021) — Show abstract
  3. SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate.
    Ducuing H, Gardette T, Pignata A, Kindbeiter K, Bozon M, Thoumine O, Delloye-Bourgeois C, Tauszig-Delamasure S, Castellani V.
    Elife (2020) — Show abstract
  4. A Spatiotemporal Sequence of Sensitization to Slits and Semaphorins Orchestrates Commissural Axon Navigation.
    Pignata A, Ducuing H, Boubakar L, Gardette T, Kindbeiter K, Bozon M, Tauszig-Delamasure S, Falk J, Thoumine O, Castellani V.
    Cell Reports (2019) — Show abstract
  5. Hijacking of Embryonic Programs by Neural Crest-Derived Neuroblastoma: From Physiological Migration to Metastatic Dissemination.
    Delloye-Bourgeois C, Castellani V.
    Front Mol Neurosci. (2019) — Show abstract
  6. Septin functions during neuro-development, a yeast perspective
    Falk J, Boubakar L, Castellani V.
    Curr Opin Neurobiol (2019) — Show abstract
  7. Commissural axon navigation in the spinal cord: A repertoire of repulsive forces is in command.
    Ducuing H, Gardette T, Pignata A, Tauszig-Delamasure S, Castellani V.
    Semin Cell Dev Biol. (2019) — Show abstract
  8. Microenvironment-Driven Shift of Cohesion/Detachment Balance within Tumors Induces a Switch toward Metastasis in Neuroblastoma.
    Delloye-Bourgeois C, Bertin L, Thoinet K, Jarrosson L, Kindbeiter K, Buffet T, Tauszig-Delamasure S, Bozon M, Marabelle A, Combaret V, Bergeron C, Derrington E, Castellani V.
    Cancer Cell (2017) — Show abstract
  9. Molecular Memory of Morphologies by Septins during Neuron Generation Allows Early Polarity Inheritance.
    Boubakar L, Falk J, Ducuing H, Thoinet K, Reynaud F, Derrington E, Castellani V.
    Neuron (2017) — Show abstract
  10. Genetic specification of left-right asymmetry in the diaphragm muscles and their motor innervation.
    Charoy C, Dinvaut S, Chaix Y, Morlé L, Sanyas I, Bozon M, Kindbeiter K, Durand B, Skidmore JM, De Groef L, Seki M, Moons L, Ruhrberg C, Martin JF, Martin DM, Falk J, Castellani V.
    Elife (2017) — Show abstract
  11. Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis.
    Arbeille E, Reynaud F, Sanyas I, Bozon M, Kindbeiter K, Causeret F, Pierani A, Falk J, Moret F, Castellani V.
    Nature Communications (2015) — Show abstract
  12. PlexinA1 is a new Slit receptor and mediates axon guidance function of Slit C-terminal fragments.
    Delloye-Bourgeois C, Jacquier A, Charoy C, Reynaud F, Nawabi H, Thoinet K, Kindbeiter K, Yoshida Y, Zagar Y, Kong Y, Jones YE, Falk J, Chédotal A, Castellani V.
    Nature Neuroscience (2014) — Show abstract

Funding & Support

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Past funding

  • European Research CouncilEuropean Research Council