Midas Anijs defends thesis on 31 January

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Neurodevelopmental disorders that affect speech and language development have complex molecular origins. At the genetic level, these disorders are likely to involve contributions from multiple genes or genetic risk factors. When looking at patients carrying pathogenic mutations in the same gene, there can be remarkable variation in their observable outcomes. The aim of this thesis was to understand how genes that are implicated in developmental speech and language disorders influence human neuronal features.

The work in this thesis has focussed on the neurodevelopmental roles and molecular networks of two candidate language-related genes: CNTNAP2 and ARHGEF39. Individuals that carry mutations in CNTNAP2 from both parents have a wide range of varying symptoms, including language impairment. Experiments with lab-grown networks of human neurons showed that long and short versions of the CNTNAP2 protein have different expression patterns and highlighted changes in the composition of molecular networks that regulate specific cell functions. Variation in ARHGEF39 has been identified as risk factor for developmental language disorder. High resolution data from prenatal human brains showed that ARHGEF39 is specifically expressed in proliferating cells in the developing neocortex. These new insights into the molecular networks around CNTNAP2 and ARHGEF39 result in hypotheses about neurobiological mechanisms relevant for variation in neurodevelopmental disorders that affect speech and language development.