The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinallayers of embryo and adult mouse brain: Increased expression in N-CAM-deficient mice

The germinative ventricular zone of embryonic brain contains neural lineage progenitor cells that give rise to neurons, astrocytes and oligodendrocyte s. The ability to generate neurons persists at adulthood in restricted brai n areas. During development, many growth factors exert their effects by int eracting with tyrosine kinase receptors and activate the phosphatidylinosit ol 3-kinase and the Ras/MAP kinase pathways. By its ability to modulate the se pathways, the recently identified Src homology 2 domain-containing inosi tol polyphosphate 5-phosphatase 2, SHIP2, has the potential to regulate neu ronal development. Using in situ hybridization technique with multiple synt hetic oligonucleotides, we demonstrated that SHIP2 mRNA was highly expresse d in the ventricular zone at early embryonic stages and subventricular zone s at latter stages of brain and spinal cord and in the sympathetic chain. N o significant expression was seen in differentiated fields. This restricted expression was maintained from embryonic day 11.5 to birth. In the periphe ry, large expression was detected in muscle and kidney and moderate express ion in thyroid, pituitary gland, digestive system and bone. In the adult br ain, SHIP2 was mainly restricted in structures containing neural stem cells such as the anterior subventricular zone, the rostral migratory stream and the olfactory tubercle. SHIP2 was also detected in the choroid plexuses an d the granular layer of the cerebellum. The specificity of SHIP2 expression in neural stem cells was further demonstrated by (i) the dramatic increase in SHIP2 mRNA signal in neural cell adhesion molecule (N-CAM)-deficient mi ce, which present an accumulation of progenitor cells in the anterior subve ntricular zone and the rostral migratory stream, (ii) the abundant expressi on of 160-kDa SHIP2 by western blotting in proliferating neurospheres in cu lture and its downregulation in non-proliferating differentiated neurospher es. In conclusion, the close correlation between the pattern of SHIP2 expressio n in the brain and the proliferative and early differentiative events sugge sts that the phosphatase SHIP2 may have important roles in neural developme nt. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.