Final Report Summary - INTERDEVO (Gene networks in cortical interneuron development: modeling interneuron function in health and disease)
The neural assembly underlying the formation of functional networks in the cerebral cortex constitutes one of the most complex neuronal systems in the brain. Much of this complexity arises during development through the interaction of two distinct neuronal types, the glutamatergic projection neurons and aminobutyric containing (GABAergic) interneurons. Recently, interneuron dysfunction has been associated with severe neurological and psychiatric disorders (e.g. epilepsy, schizophrenia and bipolar disorder). In order to achieve true progress in the understanding of cortical development and of neurological diseases associated with cortical interneuron dysfunction, a complete account of the development of its neuronal constituents is essential. In that sense, despite the detailed picture that is emerging about the development of cortical projection neurons, the mechanisms underlying the development of interneurons in the cerebral cortex have remained poorly defined.
The general objective of INTERDEVO was to obtain a comprehensive definition of the cellular and molecular mechanisms controlling the development of cortical interneurons. To reach this aim, we have taken a multidisciplinary approach by combining novel bioinformatic and genomics applications, cutting-edge imaging techniques, and conventional cellular, molecular and electrophysiological methodologies. In addition, we have genetically engineered new mouse models of cortical disorders involving interneuron deficiency.
The fulfillment of our objectives, from the perspective of their deliverables, has generated new knowledge, which can be measured by publications, patents and new technologies. In addition, although many of the more recent results obtained by the Consortium have not been translated yet into measurable activities, it is expected that additional publications will be derived from the INTERDEVO project in the coming months.
The major achievements of our project belong to one of the following categories:
- new knowledge on the mechanisms of cortical interneuron specification and patterning;
- new knowledge on the cellular and molecular mechanisms controlling the migration of cortical interneurons;
- new knowledge on the genetic determinants in the formation of GABAergic circuits in the cortex.
- development of new technologies and research tools.
There is increasing evidence suggesting that research on the development of cortical interneurons is fundamental for understanding the aetiology of a number of important human disorders, ranging from epilepsy or learning disabilities to major psychiatric illnesses such as schizophrenia, bipolar disorder or autism. In addition to increasing the knowledge on the basic mechanisms controlling the development of cortical interneurons, our research program has gone one step further in trying to exploit the full potential of genome information to underpin applications to human health. We believe the production of mouse models of cortical interneuron deficiency will have a clear impact on improving the diagnosis and understanding of human cortical developmental disorders.
The general objective of INTERDEVO was to obtain a comprehensive definition of the cellular and molecular mechanisms controlling the development of cortical interneurons. To reach this aim, we have taken a multidisciplinary approach by combining novel bioinformatic and genomics applications, cutting-edge imaging techniques, and conventional cellular, molecular and electrophysiological methodologies. In addition, we have genetically engineered new mouse models of cortical disorders involving interneuron deficiency.
The fulfillment of our objectives, from the perspective of their deliverables, has generated new knowledge, which can be measured by publications, patents and new technologies. In addition, although many of the more recent results obtained by the Consortium have not been translated yet into measurable activities, it is expected that additional publications will be derived from the INTERDEVO project in the coming months.
The major achievements of our project belong to one of the following categories:
- new knowledge on the mechanisms of cortical interneuron specification and patterning;
- new knowledge on the cellular and molecular mechanisms controlling the migration of cortical interneurons;
- new knowledge on the genetic determinants in the formation of GABAergic circuits in the cortex.
- development of new technologies and research tools.
There is increasing evidence suggesting that research on the development of cortical interneurons is fundamental for understanding the aetiology of a number of important human disorders, ranging from epilepsy or learning disabilities to major psychiatric illnesses such as schizophrenia, bipolar disorder or autism. In addition to increasing the knowledge on the basic mechanisms controlling the development of cortical interneurons, our research program has gone one step further in trying to exploit the full potential of genome information to underpin applications to human health. We believe the production of mouse models of cortical interneuron deficiency will have a clear impact on improving the diagnosis and understanding of human cortical developmental disorders.