Wnt7b stimulates axonal differentiation and development

NEILA, LORENA; ROSSO SILVANA

Congreso; XXXVI Reunion Anual de la Sociedad Argentina de Investigaciones en Neurociencias; 2021

Sociedad Argentina de Investigaciones en Neurociencias (SAN)

In the nervous system, the establishment and maintenance of neuronal polarization is crucial for correct development and function. This asymmetry is generated in response to intrinsic and extrinsic signaling molecules. Wnts proteins are known regulators of cell polarity and has also been shown to be a symmetry-breaking factor in proliferating cells. In this study, we set out to investigate the role of Wnt7b signaling in the polarization of hippocampal neurons. We previously showed that Wnt7b affects the establishment of neuronal polarity and axonal outgrowth since Wnt7b stimulated neurons evidenced an increase in axonal length. We then focused our attention on short time Wnt7b treatment analyzing tau-1 immunoreactivity after 6 h in vitro (HIV). Surprisingly, we found that several neurons exposed to Wnt7b showed higher tau-1 reactivity, a typical feature of axons, compared to controls. After that, we observed that Wnt7b stimulated neurons developed longer and more complex axon at 20 HIV. To go further, we examined the intracellular signaling pathway triggered by Wnt7b. Thus, Wnt proteins may signal through canonical or non-canonical pathway to modulate neuronal development and maturation. Pharmacological inhibition of JNK mediated non-canonical pathway reveals that inhibition JNK abolished Wnt7b axonal effectsConsistently, we then observed that Wnt7b treatment increases the JNK activity at the axonal growth cone. Later studies evidenced that Wnt7b also increases microtubule stability around 30% compared to controls. We hope to determine whether changes in microtubule dynamics are mediated by alterations on JNK activity.