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Projects. Life and Earth Sciences

Agenesis of the corpus callosum. Basic mechanisms and treatment

Lead Researcher:
Marta Nieto López

Research Centre:
Centro Nacional de Biotecnología (CNB). CSIC. Madrid.

Abstract: 

Marta Nieto LópezAgenesis of the corpus callosum (ACC) covers a series of rare diseases characterised by the absence of the axonal tract, which connects the two hemispheres of the brain. Innovative advances have shown the high therapeutic potential arising from the plasticity of the nervous system. Our research reveals the importance of plasticity and intrinsic excitability during the creation of the CC. Cux1 transcription factor appears to be an early cause of this process, regulating the expression of Kv1 potassium channels and the response trigger. Loss of Cux1 in the callos neurons leads to the complete elimination of its contralateral axons during postnatal development. However, activation of plasticity mechanisms and certain ion channels are sufficient to restore these connections. This gives rise to an excellent model for dissecting the basic mechanisms by which the CC is formed in connection with plasticity, so that its potential use in the treatment of ACC may be evaluated. We will explore these mechanisms in vivo in mice, establishing innovative genetic manipulation techniques in the cerebral cortex. We will analyse the windows in time and the limitations imposed by the circuit on CC capacity to reconnect based on modulation of neuronal excitability, as well as the cortical circuits surrounding callosum neurons, using histological, electrophysiological and imaging techniques. The results will open up new pharmacological and genetic pathways for treatment and counterbalance ACC patients' symptoms. They will also be relevant for other diseases which affect the axon and cerebral connectivity.



Marta Nieto López

She graduated in Chemistry from the Universidad Complutense de Madrid in 1993, and finished her doctorate under the direction of Dr. Francisco Sánchez Madrid in 1998. During her first stage as a postdoctoral researcher, she became interested in the study of the mechanisms that control the early development of the nervous system and the differentiation of neuronal stem cells. During this stage she was studying under the direction of Francios Guillemot, who was then working at the prestigious IGBMC, in Strasbourg, France. Completely fascinated by the complexity of the nervous system and most particularly by the complexity and functions of the neuronal networks in the cerebral cortex, she decided to move to Harvard University (Boston, MA, USA) to work with one of the best specialists in the cerebral cortex, Dr. Christopher A. Walsh. Both postdoctoral visits were made possible by the most prestigious international institutions (the Marie Curie Program, EMBO, The Human Frontiers Science Program (HFSP) and The Edward R. and Anne G. Lefler fellowships). She completed her postdoctoral studies in 2004 and having made major contributions to development neurobiology, returned to Spain. She started her own line of research in 2005, under the Ramón y Cajal program, and in 2008 she became a member scientist of the CSIC. She is currently studying the mechanisms which govern normal development of the cerebral cortex to understand the formation and normal working of cerebral circuits. She also intends to investigate the degree to which these processes are affected by mental illnesses and those which originate during development, to drive innovation in how they are treated. Her group has developed several models of mice and new tools for genetic manipulation.


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