RhoGTPase activity during neuronal polarization

ALFREDO CÁCERES

Cordoba

Simposio; Simposio: Wnt signaling during neuronal development.; 2012

Sociedad Argentina Investigacion Neurociencias

The development and maintenance of neuronal architecture involves a complex morphogenetic program that starts when recently born neuroblasts brake the neuronal sphere becoming asymmetric and adopting a bipolar morphology that will eventually lead to axon-dendrite formation. There is considerable interest in learning about the mechanisms underlying neuronal polarization since are central for understanding brain functioning under normal and pathological conditions. It is now clearly established that the highly dynamic remodeling and cross talk of the microtubule and actin cytoskeleton support axon formation and neuronal polarization. Small RhoGTPases family members have emerged as crucial regulators of cytoskeletal dynamics and microtubule and actin filament crosstalk. Using a combination of cell and molecular biology techniques, including imaging with RhoA biosensors, we now show that a pathway involving Lfc-RhoA and Rho Kinase, negatively regulate initial neurite formation and axon specification and outgrowth. This pathway is counterbalanced by Tctex-1, a dynein light chain, which negatively regulates Lfc to promote axon formation. Interestingly, after polarization, RhoA has a stimulatory effect on axon elongation that involves the formin mDia. Together our observations suggest that depending on the context and stage of d