LHX6, MTG8 and MTG16: functions and interactions in cortical interneuron development

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Inhibitory interneurons play pivotal roles within the cortex, the seat of higher order information processing in mammals. Defects in cortical interneurons cause neural network imbalance and can lead to seizure-based and neurodevelopmental cognitive and psychiatric impairments such as autism and schizophrenia. Genetic mutations affecting interneuron maturation and leading to cognitive dysfunction have been identified but we are far from understanding the genetic complexity of cortical interneuron development and how genetic defects can lead to disorders.There is a large diversity of interneurons in the cortex and it is largely unknown how this diversity is established in the developing embryo. We discovered two novel genes, Mtg8 and Mtg16, that function in concert with the master regulator of cortical interneuron development Lhx6 in the determination of interneuron subtypes in animal models. We aim to understand the relationship between the three genes and their specific requirements for interneuron development in the embryo. We will also examine wider genetic programs that are triggered by the action of these proteins in order to gain further insight into the genetic makeup that dictates interneuron cell identity. Ultimately, this knowledge will be invaluable not only in understanding interneuron-based developmental disorders, but also in the generation of interneurons from stem cells for use in transplantation repair therapies -a route already adopted experimentally for epileptic conditions in animal models.