FBS Colloquia No.257Cellular and Molecular Neurobiology Group

The molecular mechanism which induces remodeling of the cortico-mesencephalic tract after the unilateral cortical injury

The brain has the ability to recover function after injury by reorganizing neural circuits. After a unilateral cortical lesion, descending axons from the intact cortex project ectopically to the contralateral midbrain. However, the molecular mechanism for the compensatory remodeling remains unknown. We addressed this issue with the hypothesis that axon growth-promoting factors are expressed in the denervated midbrain to induce the ectopic projection. First, RNA-Seq analysis showed that various glial cell-related genes were upregulated in the denervated midbrain. Their functions on axonal remodeling were further examined by knocking-out the receptors of these molecules in the intact cortex, using the CRISPR/Cas9 technique in combination with an in utero electroporation technique. As a result, knockout of TrkB and Integrin beta 3 impaired the formation of compensatory projection. Taken together, our results suggest that the glial-derived factors expressed in the denervated midbrain contribute to the remodeling of the cortico-mesencephalic projection after unilateral cortical injury.