The formation of highly branched networks of communicating neurons is fundamental to all complex nervous systems.Dynamic changes of the neuronal cell morphology during development of the nervous system are supported and controlled by the actin cytoskeleton.Tropomyosins are actin-associated proteins that regulate the access and activity of other actin-associated proteins thereby regulating actin filament stability and dynamics.In our lab we study of neuronally expressed tropomyosins TmBrl, TmBr2, TmBr3 (TPM1 gene), Tm5NM1 (TPM3 gene) and Tm4 (TPM4 gene) in early neuronal morphogenesis.Were using B35 neuroblastoma cells and mouse primary hippocampal and cortical neurons to analyse the impact of tropomyosin overexpression on neurite outgrowth.Our data show that the overexpression of tropomyosins is sufficient to induce the formation of neurites which is associated with an upregulation of the neuronal differentiation marker MAP2c.Tropomyosins differentially control the branching of neurites in db cAMP stimulated B35 cells.While TmBr3 and Tm4 increase the degree of branching, TmBrl and TmBr2 did not promote the formation of neurite branches.The increase of branching in TmBr3 and Tm4 overexpressing B35 cells is associated with an increase in growth cone size and number of filopodia along these neurites which is associated with an increase in the expression level of the actin filament bundling protein fascin.Furthermore we show that increased expression of tropomyosin impacts on the mechanical properties of differentiating neuroblastoma cells in an isoform specific manner with TmBr3 decreasing cell surface elasticity and increasing deformability.These data suggest a central role for the actin-associated protein tropomyosin in neuronal differentiation and establishing of complex neuronal networks.