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

Abstract

AbstractöThe germinative ventricular zone of embryonic brain contains neural lineage progenitor cells that give rise to neurons, astrocytes and oligodendrocytes. The ability to generate neurons persists at adulthood in restricted brain areas. During development, many growth factors exert their e¡ects by interacting with tyrosine kinase receptors and activate the phosphatidylinositol 3-kinase and the Ras/MAP kinase pathways. By its ability to modulate these pathways, the recently identi¢ed Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 2, SHIP2, has the potential to regulate neuronal development. Using in situ hybridization technique with multiple synthetic oligonucleotides, we demonstrated that SHIP2 mRNA was highly expressed in the ventricular zone at early embryonic stages and subventricular zones at latter stages of brain and spinal cord and in the sympathetic chain. No signi¢cant expression was seen in di¡erentiated ¢elds. This restricted expression was maintained from embryonic day 11.5 to birth. In the periphery, large expression was detected in muscle and kidney and moderate expression in thyroid, pituitary gland, digestive system and bone. In the adult brain, 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 and the granular layer of the cerebellum. The speci¢city 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)-de¢cient mice, which present an accumulation of progenitor cells in the anterior subventricular zone and the rostral migratory stream, (ii) the abundant expression of 160-kDa SHIP2 by western blotting in proliferating neurospheres in culture and its downregulation in non-proliferating di¡erentiated neurospheres.In conclusion, the close correlation between the pattern of SHIP2 expression in the brain and the proliferative and early di¡erentiative events suggests that the phosphatase SHIP2 may have important roles in neural development. ß

A Phosphatidylinositol Lipids System, Lamellipodin, and Ena/VASP Regulate Dynamic Morphology of Multipolar Migrating Cells in the Developing Cerebral Cortex

“…In particular, SHIP2 is expressed in the developing brain, suggesting the possibility that SHIP2 may also be involved in process formation via PI(3,4)P 2 production. In situ hybridization showed strong SHIP2 expression in the VZ and SVZ, as reported previously (Muraille et al, 2001), including the MAZ (Fig. 7A, left).…”

Olfactory Receptor-Related Duplicons Mediate a Microdeletion at 11q13.2q13.4 Associated with a Syndromic Phenotype

“…table 2 genes with known functions are listed). However, none of these genes seems to have functions directly related to the condition reported for patient 251970, although INPPL1 may contribute to mental retardation, being involved in the neurite outgrowth process by regulating actin dynamics [Muraille et al, 2001;Prasad and Decker, 2005], and TBX10 might be responsible for the cleft palate through an unknown mechanism, different from the gain of function described by Bush et al [2004].…”

Discovery and Development of Small Molecule SHIP Phosphatase Modulators

“…In addition, the loss of function of caspase 3, which is the predominant caspase involved in the cleavage of the amyloid‐beta 4A precursor protein, is often associated with neuronal death in Alzheimer's disease. Given that SHIP2 is highly expressed in the brain, demonstrated regulation of caspase 3 by SHIP2 may play a role in Alzheimer's and other neurodegenerative diseases, a link that has been previously hypothesized . A second relationship between Alzheimer's disease and SHIP2 is implied from recent studies showing a link between the disease and insulin resistance, where hippocampal brain slices in Alzheimer's patients were less responsive to insulin than controls .…”