Cell adhesion and cell fate: An effective feedback loop during zebrafish gastrulation Dissertation Thesis

Author(s): Barone, Vanessa
Advisor(s): Heisenberg, Carl-Philipp
Committee Chair(s): Guet, Calin
Committee Member(s): Janovjak, Harald; Lemaire, Patrick
Title: Cell adhesion and cell fate: An effective feedback loop during zebrafish gastrulation
Affiliation IST Austria
Abstract: Cell - cell contact formation constitutes the first step in the emergence of multicellularity in evolution, thereby allowing the differentiation of specialized cell types. In metazoan development, cell - cell contact formation is thought to influence cell fate specification, and cell fate specification has been implicated in cell - cell contact formation. However, r emarkably little is yet known about whether and how the interaction and feedback between cell - cell contact formation and cell fate specification affect development. Here we identify a positive feedback loop between cell - cell contact duration, morphogen sig naling and mesendoderm cell fate specification during zebrafish gastrulation. We show that long lasting cell - cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for proper ppl cell fate sp ecification. We further show that Nodal signalling promotes ppl cell - cell contact duration, thereby generating an effective positive feedback loop between ppl cell - cell contact duration and cell fate specification. Finally, by using a combination of theore tical modeling and experimentation, we show that this feedback loop determines whether anterior axial mesendoderm cells become ppl progenitors or, instead, turn into endoderm progenitors. Our findings reveal that the gene regulatory networks leading to cel l fate diversification within the developing embryo are controlled by the interdependent activities of cell - cell signaling and contact formation.
Publication Title: IST Dissertation
Degree Granting Institution: IST Austria  
Degree Date: 2017-03-01
DOI: 10.15479/AT:ISTA:th_825
Notes: Many people accompanied me during this trip: I would not have reached my destination nor enjoyed the travelling without them. First of all, thanks to CP. Thanks for making me part of your team, always full of diverse, interesting and incredibly competent people and thanks for all the good science I witnessed and participated in. It has been a blast, an incredibly exciting one! Thanks to JLo, for teaching me how to master my pipettes and showing me that science is a lot of fun. Many, many thanks to Gabby for teaching me basically everything about zebrafish and being always there to advice, sugge st, support...and play fussball! Thank you to Julien, for the critical eye on things, Pedro, for all the invaluable feedback and the amazing kicker matches, and Keisuke, for showing me the light, and to the three of them together for all the good laughs we had. My start in Vienna would have been a lot more difficult without you guys. Also it would not have been possible without Elena and Inês: thanks for helping setting up this lab and for the dinners in Gugging. Thanks to Martin, for helping me understand the physics behind biology. Thanks to Philipp, for the interest and advice, and to Michael, for the Viennise take on things. Thanks to Julia, for putting up with being our technician and becoming a friend in the process. And now to the newest members of th e lab. Thanks to Daniel for the enthusiasm and the neverending energy and for all your help over the years: thank you! To Jana, for showing me that one doesn’t give up, no matter what. To Shayan, for being such a motivated student. To Matt, for helping out with coding and for finding punk solutions to data analysis problems. Thanks to all the members of the lab, Verena, Hitoshi, Silvia, Conny, Karla, Nicoletta, Zoltan, Peng, Benoit, Roland, Yuuta and Feyza, for the wonderful atmosphere in the lab. Many than ks to Koni and Deborah: doing experiments would have been much more difficult without your help. Special thanks to Katjia for setting up an amazing imaging facility and for building the best team, Robert, Nasser, Anna and Doreen: thank you for putting up w ith all the late sortings and for helping with all the technical problems. Thanks to Eva, Verena and Matthias for keeping the fish happy. Big thanks to Harald Janovjak for being a present and helpful committee member over the years and to Patrick Lemaire f or the helpful insight and extremely interesting discussion we had about the project. Also, this journey would not have been the same without all the friends that I met in Dresden and then in Vienna: Daniele, Claire, Kuba, Steffi, Harold, Dejan, Irene, Fab ienne, Hande, Tiago, Marianne, Jon, Srdjan, Branca, Uli, Murat, Alex, Conny, Christoph, Caro, Simone, Barbara, Felipe, Dama, Jose, Hubert and many others that filled my days with fun and support. A special thank to my family, always close even if they are kilometers away. Grazie ai miei fratelli, Nunzio e William, e alla mia mamma, per essermi sempre vicini pur vivendo a chilometri di distanza. And, last but not least, thanks to Moritz, for putting up with the crazy life of a scientist, the living apart for so long, never knowing when things are going to happen. Thanks for being a great partner and my number one fan!
Open access: yes (repository)