Feline Lindhout

1 20 of mature axons, this thesis uncovers new roles for the ER in modulating presynaptic function. In Chapter 2 , the dynamic transition of early neurodevelopmental stages in human iPSC- derived neurons are quantitatively and qualitatively profiled at a molecular and cellular level. This also includes a detailed characterization of axonal and dendritic microtubule remodeling processes in developing human neurons. By investigating the sequential processes during axon formation in human neurons, we demonstrate that initial axon formation follows a global distal-to-proximal reorganization in growing axons. Chapter 3 provides new insights in the role of centrosomes during the onset of axon formation in human neurons. Centrosomes display MTOC functions during this initial axon developmental process, and this is particularly important for dynamic microtubule remodeling in growing axons and subsequent axon functioning. In Chapter 4 , we explore the implication of ER structure and dynamics in presynaptic function. We report a specific interaction between ER receptor VAP and the newly identified VAP-associated protein SCRN1. The VAP-SCRN1 interactions are indispensable for ER integrity and remodeling as well as Ca 2+ -induced synaptic vesicle recycling. Finally, Chapter 5 concludes this thesis by placing the key results in a broad perspective and by laying-out important research questions for future perspectives. ACKNOWLEDGEMENTS I would like to thank Sybren Portegies for co-producing the illustrations, and Harold MacGillavry, Robbelien Kooistra and Nicky Scheefhals for their constructive feedback on the text.