RT Journal Article SR Electronic T1 Neuregulin Signaling Regulates Neural Precursor Growth and the Generation of Oligodendrocytes In Vitro JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4740 OP 4751 DO 10.1523/JNEUROSCI.21-13-04740.2001 VO 21 IS 13 A1 Viviane Calaora A1 Bernard Rogister A1 Keren Bismuth A1 Kerren Murray A1 Heidi Brandt A1 Pierre Leprince A1 Mark Marchionni A1 Monique Dubois-Dalcq YR 2001 UL http://www.jneurosci.org/content/21/13/4740.abstract AB Neuregulin 1 (Nrg-1) isoforms have been shown to influence the emergence and growth of oligodendrocytes, the CNS myelin-forming cells. We have investigated how Nrg-1 signaling of ErbB receptors specifically controls the early stages of oligodendrocyte generation from multipotential neural precursors (NPs). We show here that embryonic striatal NPs express multiple Nrg-1 transcripts and proteins as well as their specific receptors, ErbB2 and ErbB4, but not ErbB3. The major isoform synthesized by striatal NPs is a transmembrane type III isoform called cysteine-rich domain Nrg-1. To examine the biological effect of Nrg-1, we added soluble ErbB3 (sErbB3) to growing neurospheres. This inhibitor of Nrg-1 bioactivity decreased mitosis of NPs and increased their apoptosis, resulting in a significant reduction in neurosphere size and number. When NPs were induced to migrate and differentiate by adhesion of neurospheres to the substratum, the level of type III isoforms detected by RT-PCR and Western blot decreased in parallel with a reduction in Nrg-1 fluorescence intensity in differentiating astrocytes, neurons, and oligodendrocytes. Pretreatment of growing neurospheres with sErbB3 induced a threefold increase in the proportion of oligodendrocytes generated from NPs migrating out of the neurosphere. This effect was not observed with an unrelated soluble receptor. Addition of sErbB3 during NP growth and differentiation enhanced oligodendrocyte maturation as shown by expression of galactocerebroside and myelin basic protein. We propose that both type III Nrg-1 signaling and soluble ErbB receptors modulate oligodendrocyte development from NPs.