Unicentre CH-1015 Lausanne http://serval.unil.ch Year : 2012 SOURCE, FATE AND FUNCTION OF EARLY GLIAL CELLS EXPRESSING NKX2.1 IN MOUSE EMBRYONIC BRAINS VALLOTON Delphine VALLOTON Delphine, 2012, SOURCE, FATE AND FUNCTION OF EARLY GLIAL CELLS EXPRESSING NKX2.1 IN MOUSE EMBRYONIC BRAINS Originally published at : Thesis, University of Lausanne Posted at the University of Lausanne Open Archive. http://serval.unil.ch Droits d’auteur L'Université de Lausanne attire expressément l'attention des utilisateurs sur le fait que tous les documents publiés dans l'Archive SERVAL sont protégés par le droit d'auteur, conformément à la loi fédérale sur le droit d'auteur et les droits voisins (LDA). A ce titre, il est indispensable d'obtenir le consentement préalable de l'auteur et/ou de l’éditeur avant toute utilisation d'une oeuvre ou d'une partie d'une oeuvre ne relevant pas d'une utilisation à des fins personnelles au sens de la LDA (art. 19, al. 1 lettre a). A défaut, tout contrevenant s'expose aux sanctions prévues par cette loi. Nous déclinons toute responsabilité en la matière. Copyright The University of Lausanne expressly draws the attention of users to the fact that all documents published in the SERVAL Archive are protected by copyright in accordance with federal law on copyright and similar rights (LDA). Accordingly it is indispensable to obtain prior consent from the author and/or publisher before any use of a work or part of a work for purposes other than personal use within the meaning of LDA (art. 19, para. 1 letter a). Failure to do so will expose offenders to the sanctions laid down by this law. We accept no liability in this respect. Département de Biologie Cellulaire et Morphologie SOURCE, FATE AND FUNCTION OF EARLY GLIAL CELLS EXPRESSING NKX2.1 IN MOUSE EMBRYONIC BRAINS Thèse de doctorat en Neurosciences présentée à la Faculté de Biologie et de Médecine de l’Université de Lausanne par Delphine VALLOTON Biologiste diplômée de l’Université de Lausanne, Suisse Jury Prof. Philippe Maeder, Président Dr. Cécile Lebrand, Directrice Prof. Jean-Pierre Hornung, Co-directeur Dr. Sonia Garel, Experte Prof. Alexandre Dayer, Expert Lausanne 2012 Programme doctoral interuniversitaire en Neurosciences des Universités de Lausanne et Genève 1 2 ACKNOWLEDGMENTS The first person I would like to thank a lot is of course my thesis director Cécile, who accepted to take me in her lab 5 years ago, for performing my master work first, what led then to these exciting thesis studies with a lot of sudden revivals. So, thank you, Cécile, for giving me such a great opportunity to achieve my PhD in your team. Thank you also for sharing the so many skills you possess in “Science”, for your dynamism, for your enthousiasm and tenacity, and all the time and energy you have given to offer me a favorable and prosperous thesis environment. Thanks for your availability, for the understanding you have shown and for the support you have given to me when I had doubts. Finally, thank you for this unforgettable and emotionally rich adventure. I would like also to thank Jean-Pierre Hornung for his dedicated support and for kindly welcoming me and for sharing his lab space and equipment since the very beginning of my master until the very last moments of my PhD studies. Many thanks also for sharing your scientific knowledge and for your wise advices on many aspects of our research. Thank you also to all the members of my master, half-thesis and thesis jury who kindly accepted to review my work many times through the last years. Thanks for the time you have offered and that you offer again, and for your scientific remarks. Then, I would like to thank a few teams: The Lebrand’s team in which I am proud to be the second studient and maybe unfortunately… the last to end its thesis studies, and in which I feel like I had the chance to be guided by two pionnering axo… members. Ladies first, so thanks to Christiane for her kindness and who has taken care of our psychological and unmaterial concerns with gentleness, for her technical and unmeasurable help in molecular biology; to Carine for all the working hours that you made so nice to go through, for all the fun, for all the laugh we had inside and out of the lab and for your endless creativity that just started to emerge in our first Christmas costumes and for giving me so often the account of your advantures; to Shilpi for her enormous investment and quick acclimatization in the work of the lab and for her brilliant to visionnary skills and knowledge in science, but also for many gales of laughter and for our good indian and greek food sessions. And then the guys, so thanks to Sebastien and Mathieu who both gave me the impulse to choose the Lebrand’s team, to Belkacem who shared also with us nearly one year of its life in the lab and also many beers and parties outside of the lab. The Hornung’s team Thank you Dominique for your kindness, for your availability, for teaching me also a piece of your expertise in histology and thanks also for the nice chats during the long hours of dissection, cutting or mounting the brain slices. Then thanks to all the past and present members of the lab, so thank you Natacha, Peggy, Mary-Aude, Christine, Lionel, Alessandro, Julien and Alex and for all the fun we had and thank you everyone for making this journey enjoyable. I would like also to give a special big Thanks to both teams together, for your presence and your support at all the dance shows and Christmas choreography I gave during the last five years since I think they were around 9! Thanks also to all the members of the DBCM, 3 Fanny, Alain and all the members of the animal facility for taking care of our mice, Alex Sandoval and Yannick for informatical help, Eric for the printing of the posters and manuscript, Rudolf for its precious help in statistics and the secretariat team. I would like also to thank some other people and teams that brought help in many ways So thanks to: Jean-Luc Martin and Hubert Fiumelli who gave me the opportunity to start in their team for my pre-master work during which I already learned a lot, and a special thank to Hubert who taught us and set up the equipment for the In Utero electroporation. Jean-Yves Chatton and the CIF team for teaching me THE confocal microscopy, Christophe Lamy for helping me to give practicals in confocal microscopy and for sharing his knowledge in live imaging. Yvan Arsenijevic for the neurosphere’s technique. Sonia Bolea, Sonia Garel, Alexandre Dayer, Denis Jabaudon, Victor Borrell, Gord Fishell, Oscar Marin, for their encouragements, advises and support. Then I would like to thank more intimately some colleagues: To all guys of the coffee and apero corner, thank you for your kindness, availability, happiness and humanity and for everything you have done to make the work place more warm, funny, lively and welcoming. Thank you Jannick, Nieves, Nicole, Marie, Guylène, Saska, Sanda, Maria, Francine, Shilpi, the Romanette’s, Dimitri, Guy, Charles, Denis, Gilles, Alessandro, Hadi, David, Evrim… To Peter Clarke and all the Christmas party staff: The dancers and acrobats: Shilpi, Saska, Nicole, Franceline, Marie, Guylène, Christine, Tugce, Nieves, Jannick, Maria, Francine, Carine, Sanda, Valeria, Michel, Alex, Dimitri, Guy, Donald. Two rock bands: A great thank to Michel Kielar our spiritual guide and musical leader, to Matthieu for the equipment and the drums, to Christophe for the guitar bass, to Mathieu and Dutch for the folk guitar and vocals and to Lily for the outstanding vocal performance. Finally, I would like to thank my friends and family who largely contribute to this adventure. Thank you, my Friends of Ever, Marylaure, Simone and Sonia for the years of friendship. Thank you for being here at any time. Thank you, my dancing friends and teachers, Jean-Philippe, Marion, Héloïse, Baronne, Alice, Gwendolyn, Marinaz, Daniela, and so many others… Thank you, my friends from le gymnase du soir, Carine, Aurore, Amanny, Stephane, Sophie and Manu. Thank you, my new friends, Lily, Laurent, Damien, Alex and Dutch. Thank you, my parents and my brother, for taking care of me since ever. Thank you, my new family. And finally, Thank You, Mathieu, to have taken me as your Padawan in science, but more importantly to protect me, to support me, to daily share your feelings and emotions with me, and to share a big piece of life with me. 4 ABSTRACT Source, fate and function of early glial cells expressing Nkx2.1 in mouse embryonic brains Delphine Valloton Department of Cellular Biology and Morphology The brain tissue is made of neuronal and glial cells generated in the germinal layer bordering the ventricles. These cells divide, differentiate and migrate following specific pathways. The specification of GABAergic interneurons and glutamatergic neurons has been broadly studied but little is known about the origin, the fate and the function of early glial cells in the embryonic telencephalon. It has been commonly accepted since long that the glial cells and more particularly the astrocytes were generated after neurogenesis from the dorsal telencephalon. However, our work shows that, unlike what was previously thought, numerous glial cells (astroglia and polydendrocytes) are generated during neurogenesis in the early embryonic stages from E14.5 to E16.5, and originate from the ventral Nkx2.1-expressing precursors instead. NK2 homeobox 1 (Nkx2.1) is a member of the NK2 family of homeodomain- containing transcription factors.