Embryonic neuro-development and childhood cancers

Principal investigator: Valérie CASTELLANI

embryogenesis | developmental biology | pediatric cancers | cell migration | metastasis | axon guidance | microenvironment

 We study mechanisms underlying embryonic neurodevelopment and malignancies of prenatal origin.

Our laboratory studies the cellular and molecular mechanisms that control the formation of the nervous system in the embryo. We are interested in the communication of progenitor and neuronal cells with their environment, with a focus on the cellular processes and molecular signaling that control the colonization of embryonic territories by migrating neural cells and axons. We are currently addressing these questions by studying a remarkable embryonic cell population, the neural crest, at the origin of multiple derivatives, including the sympathetic chain, adrenal medulla, and enteric nervous system. Using experimental manipulations in the avian embryo model and transcriptomics, we study the emergence of enteric neural circuits and brain-gut connectivity to characterize the gene programs that mediate communication between cells and their environment. We are investigating whether these programs are conserved in the human embryo and whether their deregulation might contribute to gut neurodevelopmental disorders.

In parallel, we study pediatric cancers in the light of their embryonic origin, in particular neural crest derived neuroblastoma and cerebellar precursor-derived medulloblastoma. The heterogeneity and plasticity that characterize these malignancies and underlie their aggressiveness are thought to be rooted in the embryonic context of their emergence. Tumorigenic events take place in cells that actively communicate with their environment and are endowed with the proliferative and migratory properties necessary for tissue formation.

While becoming malignant, tumoral cells retain many of the characteristics of the cells of origin. Our goal is to understand how during tumorigenesis and metastasis this dual physiological and tumorigenic potential is manifested by the opportunistic exploitation or hijacking of developmental mechanisms and signaling pathways. This basic research will pave the way for the development of therapies that specifically target tumor-specific behavior and signaling. To address these questions, and taking advantage of our developmental biology models, we have established a specific in vivo paradigm that recapitulates the embryonic context for malignant cells. It consists of transplanting human tumor cells into selected tissues of the avian embryo. Our studies are based on a multi-approach strategy combining experimental embryology, functional studies of genes of interest in avian models, 3D light sheet microscopy to map cells and molecules at the whole embryo level, videomicroscopy, and large-scale transcriptomic analyses.


For the general public

How are our neural circuits built? 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 postnatal development, millions of axons go in search of their partners, some remaining confined to the brain or spinal cord, others colonizing the whole organism to innervate the muscles, the skin, the viscera. Many neuronal cells also migrate to colonize distal territories where they will form a nervous structure. Molecular signals are expressed in embryonic tissues that allow axons and cells to locate themselves in space. They are called topographic or guidance signals. Getting each axon and cell to its destination is a real challenge, and it is these processes that our team is studying. Can axons and cells get lost or misdirected along the way? Alterations of cell and axon migration are responsible for childhood pathologies. Many remain undiscovered because the identification of alterations of these early processes remains difficult. Cells can also become malignant prenatally, at a time when they are undergoing migration and proliferation. They give rise to tumors that can be highly metastatic and have a poor outcome. Our team studies the behavior of malignant cells and how they communicate with embryonic tissues during tumorigenesis and metastasis.


South-ROCK Our team is a member of the South-ROCK integrated research center of excellence in pediatric oncology of Lyon-Marseille, one of the three laureates of the French National Cancer Institute's PEDIACRIEX call for projects.


REACT4Kids Our team is part of REACT4KIDS (REsearchers in oncology ACTing for kids), a national collaborative network of pediatric oncology research laboratories whose goal is to foster collaborative research for gaining knowledge about the biology of childhood cancers to pave the way for innovative therapies tailored to these cancers.

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.

Team Members

  • Valérie CASTELLANIResearcher CNRS, HDR – valerie.castellani@univ-lyon1.fr
  • Frédéric MORETAssistant Professor, UCBL, HDR – frederic.moret@univ-lyon1.fr
  • Julien FALKResearcher, CNRS, HDR – julien.falk@univ-lyon1.fr
  • Servane TAUSZIG-DELAMASUREResearcher, CNRS, HDR – servane.tauszig-delamasure@univ-lyon1.fr
  • Maëva LUXEYAssistant Professor, UCBL – maeva.luxey@unibas.ch
  • Muriel BOZONResearch Assistant, CNRS – muriel.bozon@univ-lyon1.fr
  • Karine THOINETResearch Assistant, CNRS – karine.thoinet@univ-lyon1.fr
  • Franck BOISMOREAUPost-doc, UCBL – franck.boismoreau@univ-lyon1.fr
  • Audrey PRUNETPost-doc – audrey.prunet@univ-lyon1.fr
  • Maëlys ANDREPhD student, UCBL – maelys.andre@univ-lyon1.fr
  • Raphael GURYPhD Student – raphael.gury@univ-lyon1.fr
  • Marion MALLETPhD Student – marion.mallet@univ-lyon1.fr
  • Luce ROSEIROPhD Student – luce.roseiro@univ-lyon1.fr
  • Florian MARTINResearch Assistant – florian.martin@univ-lyon1.fr
  • Emy THEOULEResearch Assistant, UCBL – emy.theoulle@univ-lyon1.fr
  • Karine THOINETResearch Assistant, CNRS – karine.thoinet@univ-lyon1
  • Cécile FAURE-CONTEROncopédiatre IHOPe, CLB – cecile.conter@ihope.fr
  • Jérémy GANOFSKYBioinformatician – jeremy.ganofsky@univ-lyon1.fr


  • Céline Delloye-BourgeoisGroup leader, Center of Research of Cancerology of Lyon, France
  • Homaira Nawabi Group leader, Grenoble Institute of Neuroscience, France
  • Camille CharoySenior microscopist at The Francis Crick Institute, UK
  • Florie ReynaudResearch Engineer, Center of Research of Cancerology of Lyon, France
  • Elise ArbeilleAssistant professor, University of Méditerranée, Marseille, France
  • Anne Briançon-MarjolletAssistant professor, Grenoble-Alpes University, Grenoble, France

Selected publications

  1. Functional precision oncology for follicular lymphoma with patient-derived xenograft in avian embryos.
    Zala M, Lipinski B, Costechareyre C, Jarrosson L, Teinturier R, Julia E, Lacourrège M, Verney A, Guitton J, Traverse-Glehen A, Bachy E, Salles G, Huet S, Genestier L, Castellani V, Delloye-Bourgeois C, Sujobert P.
    Leukemia (2024) — Show abstract
  2. An in vivo avian model of human melanoma to perform rapid and robust preclinical studies
    Jarrosson L, Dalle S, Costechareyre C, Tang Y, Grimont M, Plaschka M, Lacourrège M, Teinturier R, Le Bouar M, Maucort-Boulch D, Eberhardt A, Castellani V, Caramel J, Delloye-Bourgeois C.
    EMBO Mol Med. (2023) — Show abstract
  3. A balance of noncanonical Semaphorin signaling from the cerebrospinal fluid regulates apical cell dynamics during corticogenesis.
    Gerstmann K, Kindbeiter K, Telley L, Bozon M, Reynaud F, Théoulle E, Charoy C, Jabaudon D, Moret F, Castellani V.
    Sci Advances (2022) — Show abstract
  4. GPC3-Unc5 receptor complex structure and role in cell migration
    Akkermans O, Delloye-Bourgeois C, Peregrina C, Carrasquero-Ordaz M, Kokolaki M, Berbeira-Santana M, Chavent M, Reynaud F, Raj R, Agirre J, Aksu M, White ES, Lowe E, Ben Amar D, Zaballa S, Huo J, Pakos I, McCubbin PTN, Comoletti D, Owens RJ, Robinson CV, Castellani V, Del Toro D, Seiradake E.
    Cell (2022) — Show abstract
  5. Environmental cues from neural crest derivatives act as metastatic triggers in an embryonic neuroblastoma model.
    Ben Amar D, Thoinet K, Villalard B, Imbaud O, Costechareyre C, Jarrosson L, Reynaud F, Novion Ducassou J, Couté Y, Brunet JF, Combaret V, Corradini N, Delloye-Bourgeois C, Castellani V.
    Nature Communications (2022) — Show abstract
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. Septin functions during neuro-development, a yeast perspective
    Falk J, Boubakar L, Castellani V.
    Curr Opin Neurobiol (2019) — Show abstract
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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

La Ligue

Past funding

  • European Research CouncilEuropean Research Council