INTERMMOODEL · Generation of Inter-neuron deficient mouse model
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2010-04-15 → 2011-04-14
- EU contribution
- €83,275
- Participants
- 1
- Scheme
- IIF
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Results in brief
Final Activity and Management Report Summary - INTERMMOODEL (Generation of Interneuron deficient mouse model)
The general objective of INTERMMOODEL was to obtain a definition of the cellular and molecular mechanisms controlling the development of cortical interneurons. To reach this aim, we took a multidisciplinary approach by combining genomic applications, conventional cellular, molecular and electrophysiological methodologies. To determine the contribution of temporal segregation in the generation of cortical interneuron diversity, we generated transgenic mice lines that allowed to permanently tracing the progeny of distinct interneuronal progenitors. Different mice lines were produced in which the expression of Cre recombinase is restricted to subpallial progenitors of cortical interneurons. For this purpose, we produced BAC transgenes using recombineering technology to insert a Cre recombinase (Cre) under the control of selected transcription factor promoters like Nkx5-1, Nkx6-2 and Pax6. The three lines contribute with progenitors derivatives to different areas of the mouse brain. Using the Nkx5-1-Cre line we were able to show that the preoptic area (POA), is a novel source of cortical GABA-ergic interneurons in the mouse. Genetic lineage-tracing experiments demonstrated that neurons born in the POA migrate to the neocortex and hippocampus, where they differentiate into a distinct population of GABA-ergic interneurons with relatively uniform neurochemical, morphological and electrophysiological properties. By the Pax6 Cre line we were able to identify how some neurons migrate to integrate into an area of the brain to conform the Globus Pallidus. By means of a Dbx1 Cre line, we were able to identify that the POA were capable of producing a highly diverse population od interneuron that migrates to the cortex.
Data: CORDIS, © European Union
Project objective
The neural circuits underlying the formation of functional networks in the cerebral cortex constitute one of the most complex physical systems in the World. Much of this complexity arises during development through the interaction of two distinct neuronal types, 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 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 goal of this project is to obtain a comprehensive definition of the cellular and molecular mechanisms controlling the development of cortical interneurons.To reach this aim, I propose to take a multidisciplinary approach by combining mouse genetics, novel genomic applications, cutting-edge imaging techniques, and conventional cellular and molecular biology methodologies. In addition, I will develop new genetic tools to engineer developmental models of cortical disorders involving interneuron deficiency.Thus, successful execution of the project will result in:i) New knowledge of the mechanisms underlying the specification, migration and differentiation of cortical interneurons, andii) Generation of new developmental models of cortical disorders resulting from interneuron deficiency.
Original text from CORDIS.
Participants
- INSTITUTE FOR GENETIC ENGENIERING AND MOLECULAR BIOLOGY · BUENOS AIRESCoordinatorCity levelArgentina
Links
Data: CORDIS, © European Union