Thesis defense Aron Kos (Donders series 248)
8 November 2016
Promotors: prof. dr. H. van Bokhoven, prof. dr. G. Martens
Copromotors: dr. A. Aschrafi, dr. S. Kolk
Regulation of cortical neuronal development by microRNA-controlled gene networks
The brain is an intricate organ and serves as the centre of the nervous system, responsible for receiving and processing information. It is made up of a plethora of different cell types, strictly organized into specialized areas fulfilling specific functions. The numerous neural cells within the brain form intricate networks through the outgrowth of axons and dendrites, which have extensive ramifications that are engaged in neural connectivity through synaptic connections. One of the largest specialized areas within the brain is the cerebral cortex, which is responsible for a number of crucial cognitive functions including memory, perception, awareness and consciousness. The correct formation of this brain area is critically important for its ability of properly executing its functions. Indeed, malformations of the cortex are associated with a range of neurodevelopmental disorders such as intellectual disability, schizophrenia and autism spectrum disorders. To understand these disorders one needs to understand the underlying regulatory molecular networks responsible for the formation, maintenance and plasticity of the cortex. One critical group of regulatory genes are microRNAs (miRs). An increasing body of evidence have implicated miR expression changes with a number of neurodevelopmental disorders. miRs are non-coding genes that generate short RNA molecules, which can regulate translational repression and mRNA destabilization upon binding to complementary sequences within mRNA transcripts. Due to the critical impact of miR regulation on cortical development we aimed in the current thesis to identify miRs which have the capacity to control key aspects of cortical neurodevelopment such as axon, dendrite growth and synapse development.