Project title: Investigating cooption of developmental programs in a chick model of medulloblastoma
Type of rotation: M2 (6 months)
Supervisors: Cédric Maurange and Mehdi Saadaoui
Concept and Objectives
Pediatric cancers are rare and remain poorly understood. They are often initiated during specific embryonic or fetal developmental windows. However, it is still unclear why embryonic/fetal cells are particularly prone to initiate tumorigenesis. In the team, we use various animal models to investigate how developmental programs are coopted from specific cells to initiate tumorigenesis during early developmental stages (1-4).
During this M2 project, the student will work on a recently developed model of medulloblastoma (the most common brain tumor in children) in the chick embryo. The chick embryo has the advantage of being easily accessible for genetic manipulations and of causes fewer ethical concerns than other animal models. The student will build on new spatial transcriptomic data performed in the lab to decipher which gene regulatory networks are coopted upon mis-expression of major oncogenes to cause tumor initiation. During this project the student will use diverse techniques such as electroporation, immunostaining, molecular biology and imaging techniques.
References
1: Gaultier C, Foppolo S, Maurange C. Regulation of developmental hierarchy in Drosophila neural stem cell tumors by COMPASS and Polycomb complexes. Sci Adv. 2022 May 13;8(19):eabi4529. doi: 10.1126/sciadv.abi4529. Epub 2022 May 11. PMID: 35544555; PMCID: PMC9094666.
2: Maurange C. Temporal patterning in neural progenitors: from Drosophila development to childhood cancers. Dis Model Mech. 2020 Jul 22;13(7):dmm044883. doi: 10.1242/dmm.044883. PMID: 32816915; PMCID: PMC7390627.
3: Genovese S, Clément R, Gaultier C, Besse F, Narbonne-Reveau K, Daian F, Foppolo S, Luis NM, Maurange C. Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors. Elife. 2019 Sep 30;8:e50375. doi: 10.7554/eLife.50375. PMID: 31566561; PMCID: PMC6791719.
4: Narbonne-Reveau K, Lanet E, Dillard C, Foppolo S, Chen CH, Parrinello H, Rialle S, Sokol NS, Maurange C. Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila. Elife. 2016 Jun 14;5:e13463. doi: 10.7554/eLife.13463. PMID: 27296804; PMCID:PMC4907696.