The effects of B-RAF kinase signaling on axon development, regeneration and sensory function

18 settembre 2015
18th September 2015
Contatti: 

Venue: Edificio Povo 2, via Sommarive nr. 9, Povo (Tn) - Room B101
 at 2:00 p.m.

  • Jian Zhong -  Brain and Mind Research Institute, Cornell University , Molecular Regeneration and Neuroimaging Laboratories, Burke Medical Research Institute.

In mammalian embryos, axons grow vigorously and precisely to interconnect the nervous system, and form connections to sensory receptors, to muscles and to internal organs. In the mature nervous system, axon growth stops. After an injury, axons do regenerate (if imperfectly) in the peripheral nervous system, but no productive regeneration occurs in the central nervous system. Because of this lack of axon regeneration, spinal cord injuries, for example, result in permanent paralysis, and retinal axon degeneration in glaucoma causes irreversible loss of vision. Two reasons have been suggested for why axons cannot re-grow in the mature CNS. First, cell-intrinsic growth pathways are downregulated as the nervous system matures, and second, the mature CNS expresses surface molecules that inhibit axon growth and thereby stabilize the mature configuration. Previous work has clearly shown that injured adult neurons in the CNS can in principle re-grow axons under certain circumstances. However, such axonal regrowth or sprouting have not been able to reach their targets due to limited length and density of regenerative growth. Our current major focus is to attempt driving axon regeneration in the injured optic nerve, which is a part of the CNS, by genetic activation in mature retinal neurons of pathways that we know can drive axon growth in embryonic neurons. We use several lines of genetically modified mice that allow us to selectively activate or inactivate specific signaling molecules in the nervous system shortly before nerve injury. We then assess regeneration phenotypes using high-resolution imaging, and we test for possible recovery of visual behaviors.

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