Brain neurons and glial cells express Neu differentiation factor/heregulin: a survival factor for astrocytes.

Abstract

Neu differentiation factor (NDF, also cafled

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

“…The results of this analysis indicated that ligand expression dramatically decreased with age, whereas a parallel increase in erbB-3 expression and a concomitant moderate down-regulation of erbB-4, occurred in the ®rst 3 weeks of postnatal life ( Figure 4). This observation is consistent with the lack of signi®cant erbB-3 expression in E10.5 mouse embryos (data not shown) and the results of immunohistochemical (Pinkas-Kramarski et al, 1994), as well as in situ hybridization analyses (Chen et al, 1994) of neuregulin, whose neural expression appears to decrease, but not disappear, after birth. Possibly, ErbB-4 is the NDF receptor that mediates the major cerebellar neurogenic phase in the ®rst week of postnatal life, but ErbB-3 replaces it, at least in part, in later stages and in adult life.…”

“…Similar to the expression pattern of NDF/neuregulin in adult rat brain (Chen et al, 1994;Pinkas-Kramarski et al, 1994), both receptors were expressed in regions of the limbic and the motor systems. These include various sites in the cerebral cortex (e.g.…”

“…NDF, the ligand of ErbB-3 and ErbB-4, is predominantly expressed in the central and peripheral nervous systems, but it is also expressed in other organs, such as the adrenal gland, liver and intestine (Marchionni et al, 1993;Orr-Urtreger et al, 1993;Chen et al, 1994;Birchmeier, 1994, 1995;Pinkas-Kramarski et al, 1994;Corfas et al, 1995;Ho et al, 1995). It has been previously shown by using Northern blot analysis, that the two NDF receptors are widely expressed in various epithelial cell lines (Prigent et al, 1992;Plowman et al, 1993).…”

“…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).…”

“…The present study explored this possibility, and also addressed the e ect of neuregulins on neurons. Although this cell type often expresses neuregulins and their receptors (Meyer and Birchmeier, 1994;Pinkas-Kramarski et al, 1994;Corfas et al, 1995), and the neuron-derived ligand acts on many types of non-neuronal cells, the e ect of NDF on nerve cells has not been extensively investigated before. Here we show that the patterns of expression of the two NDF receptors are remarkably di erent: The embryonic central nervous system and heart being primary sites of ErbB-4 expression, whereas the epithelial component of various parenchymal organs and the adult nervous systems are the main locations of ErbB-3.…”