Neural stem cells from protein tyrosine phosphatase sigma knockout mice generate an altered neuronal phenotype in culture

The neurospheres from the knockout mice acquired heterogeneous developmental characteristics and they showed similar morphological characteristics to the age matched siblings. Although Ptprs expression decreases as a function of developmental age in vivo, it remains high with the continual renewal and passage of the neurospheres. Stem cells, progenitors and differentiated neurons, astrocytes and oligodendrocytes all express the gene. While no apparent differences were observed in developing neurospheres or in the astrocytes and oligodendrocytes from the PTPσ knockout mice, the neuronal migration patterns and neurites were altered when studied in culture. In particular, neurons migrated farther from the neurosphere centers and the neurite outgrowth exceeded the length of the neuronal processes from age matched sibling controls.Our results imply a specific role for PTPσ in the neuronal lineage, particularly in the form of inhibitory influences on neurite outgrowth, and demonstrate a role for tyrosine phosphatases in neuronal stem cell differentiation.Neural stem cells comprise a relatively quiescent, uncommitted and multipotent subpopulation in the central nervous system [1-3]. Stem cells reside in multiple areas of the central nervous system including the olfactory bulb, striatum, cerebellum, hippocampus (dentate gyrus), cerebral cortex and spinal cord [4]. The subventricular zone (SVZ) is one of the richest zones capable of generating stem cells during development and into old age [5]. In culture, neural stem cells and progenitor cells grow as spherical cell clusters termed neurospheres, and they provide a valuable way to investigate neuronal and glial cell lineage development in vitro. Neural stem cells express EGF and FGF receptors [6] and the mitogens FGF and EGF are used to induce mitosis in stem cells [7,8].During development, cell signaling facilitates cellular maturation as well as extracellular interactions between the cells and the environment [9]. Kinases