A role for nuclear PTEN in neuronal differentiation

Mutations of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) , a protein and lipid phosphatase, have been associated with gliomas, macro cephaly, and mental deficiencies. We have assessed PTEN's role in the nervo us system and find that PTEN is expressed in mouse brain late in developmen t, starting at approximately postnatal day 0. In adult brain, PTEN is prefe rentially expressed in neurons and is especially evident in Purkinje neuron s, olfactory mitral neurons, and large pyramidal neurons. To analyze the fu nction of PTEN in neuronal differentiation, we used two well established mo del systems-pheochromocytoma cells and cultured CNS stem cells. PTEN is exp ressed during neurotrophin-induced differentiation and is detected in both the nucleus and cytoplasm. Suppression of PTEN levels with antisense oligon ucleotides does not block initiation of neuronal differentiation. Instead, PTEN antisense leads to death of the resulting, immature neurons, probably during neurite extension. In contrast, PTEN is not required for astrocytic differentiation. These observations indicate that PTEN acts at multiple sit es in the cell, regulating the transition of differentiating neuroblasts to postmitotic neurons.