Cell positioning and neuronal network formation are crucial for proper brain function. Disrupted-in-Schizophrenia 1 (DISCI) is antero-gradely transported to the neurite tips, together with Lisl, and functions in neurite extension via suppression of GSK313 activity. Then, transported Lisl is retrogradely transported and functions in cell migration. Here, we showthat DISCl-binding zinc fingerprotein (DBZ), together with DISCl, regulates mouse cortical cell positioning and neurite development in vivo. DBZ hindered Ndell phosphorylation at threonine 2l9 and serine 25l. DBZ depletion or expression of a double-phosphorylated mimetic form of Ndell impaired the transport of Lisl and DISCl to the neurite tips and hampered microtubule elongation. Moreover, application of DISCl or a GSK313 inhibitor rescued the impairments caused by DBZ insufficiency or double-phosphorylated Ndell expression. We concluded that DBZ controls cell positioning and neurite development by interfering with Ndell from disproportionate phosphorylation, which is critical for appropriate anterograde transport of the DISCl-complex.
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