Wnt7b induces changes in axonal development through regulation of microtubule behavior.

NEILA, LORENA; ROSSO SILVANA

Virtual

Congreso; XXXV Reunion Anual de la Sociedad Argetina de Investigaciones en Neurociencias.; 2020

Sociedad Argetina de Investigaciones en Neurociencias.

In the nervous system, a proper microtubule dynamic and organization is crucial for the initiation, extension and maintenance of neurites. Wnts proteins, through different cascades, regulate cytoskeletal network and the activity of effectors to control neuronal polarity, axon and dendrite development. In this work, we focused our attention on the role of Wnt7b on earlier neuronal development, particularly on axonal growth. We previously showed that Wnt7b affects the establishment of neuronal polarity and axonal outgrowth since Wnt7b stimulated neurons evidenced increased axonal length and complexity. Importantly, we recently observed that Wnt7b increases microtubule stability (around 30%) in immature neurons compared to controls. Moreover, Wnt7b induced the formation of looped microtubules at the axonal growth cones. In next studies, we will carefully analyze the organization of microtubules in the growth cone of Wnt7b stimulated neurons. To go further, we found that pharmacological inhibition of JNK mediated pathway (PCP pathway) abolished the Wnt7b effects on axonal morphology. Consistently, we then evidenced that neurons exposed to Wnt7b show an increase in the activity of JNK. This effect was observed by immunofluoresces and Western blot approaches. In future experiments, we hope to determine whether changes in microtubule dynamics induced by Wnt7b are mediated by alterations on JNK activity.