A role for the acetylcholine receptor-inducing protein ARIA in oligodendrocyte development.

Abstract

ARIA acetylcholine receptor-inducing activity protein, is a member of a family of ligands that includes the Neu differentiation factor, heregulin, and glat growth factor. These ligands all act through one or more receptor tyrosine kinases of 4185 kDa. In some conditions these ligands promote proliferation, whereas in others they induce differentiation.ARIA was orinally isolated from chick brain on the basis of its ability to induce synthesis of nicotinic acetylcholine receptors in skeletal muscle. In this paper we show that ARIA is expressed in the subventricular zone of the rat brain and that it enhances the development of oligodendrocytes from bipotential (02A) (20,(22)(23)(24)33). In the presence of serum, 02A progenitors develop into type II astrocytes, while in the absence of serum they develop into oligodendrocytes (22). Therefore, in the absence of serum this paradigm provides a simple assay to study the influence of growth factors and cytokines on glial development.We examined the influence of ARIA on 02A cells and found that it induces properties characteristic of ofigodendrocytes. Furthermore, exposure to ARIA doubles the number ofoligodendrocytes that extend sheet-like processes. The effects of ARIA on oligodendrocyte progenitors appear to be mediated through a p185 receptor tyrosine kinase as evidenced by its phosphorylation upon treatment with ARIA similar to that seen in ARIA-treated muscle (8). In contrast to oligodendrocytes, Schwann cells respond to ARIA by increasing their mitotic rate. This is an expected result because ARIA, in addition to being homologous to the rodent Neu differentiation factor and human heregulin, is homologous to the bovine glial growth factor (GGF), a known Schwann cell mitogen (4,(9)(10)(11)(12).

Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia

“…Not only is NRG-1 and various ErbB receptors expressed in the subependymal zone and the forebrain oligogenic zone, but NRG-1 can also induce the division 43 and/or promote the differentiation of oligodendrocyte precursors in vitro. [44][45][46][47] It is conceivable that relatively decreased type II mRNA expression may relate to putative abnormalities of oligodendroglial function implicated in schizophrenia. 48,49 Finally, we did not find evidence that NRG-1 type III mRNA expression levels are changed in schizophrenia DLPFC, although this isoform also has effects on neuronal plasticity and development.…”

The myelin-pathogenesis puzzle in schizophrenia: a literature review

“…55,56 Further, NRG1 has been studied to have a key role in neurodevelopmental process in central nervous system (CNS) that includes oligodendrocyte development. 57 Therefore, we further discuss this important gene in more details in the second part of the article. Meanwhile, other genes at or close to this locus 58 have emerged as possible risk factors for schizophrenia by positional candidate gene analysis for example, calcineurin A-g subunit gene (PPP3CC), MSTP131.…”

Differential expression of NDF/neuregulin receptors ErbB-3 and ErbB-4 and involvement in inhibition of neuronal differentiation

“…An in vivo e ect on synaptic Schwann cell survival after denervation has been recently demonstrated (Trachtenberg and Thompson, 1996). Myelin-forming cells of the central nervous system, the oligodendrocytes, are also targets of NDFs/ neuregulins (Vartanian et al, 1994;Canoll et al, 1996), as are embryonic astroglia, whose maturation and survival are a ected, but not their proliferation (Pinkas-Kramarski et al, 1994). An instructive signal of neuregulin for glial di erentiation, on the expense of a neuronal fate, was demonstrated by using neural crest stem cells (Shah et al, 1994).…”