The ErbB4 neuregulin receptor mediates suppression of oligodendrocyte maturation.
Neuregulin is required for proper oligodendrocyte development, but which receptors are involved and whether neuregulin promotes or inhibits maturation remain controversial. To assess the roles of the neuregulin receptor ErbB4 in oligodendrocyte development, we examined oligodendrocyte initiation and maturation in cultures derived from erbB4 knock-out mice and rat spinal cord in the presence of neutralizing erbB4 antibodies. No differences in the development of O4+ oligodendrocytes were detected in the presence or absence of erbB4 signaling. All four epidermal growth factor receptor family members were detected in the ventral neural tube at approximately the time of initial oligodendrocyte development, consistent with redundancy in neuregulin receptor signaling at the onset of oligodendrocyte development. In contrast, greater numbers of differentiated (monoclonal antibody O1+) oligodendrocytes developed in neural tube explants from erbB4(-/-) mice than either erbB4(+/+) or erbB4(+/-) littermates as well as in cultures treated with anti-erbB4. These data indicate that ErbB4 is not required for oligodendrocyte development and, in fact, inhibits oligodendrocyte lineage maturation. Together with previous studies, these data suggest a model in which early oligodendrocyte lineage development is regulated by promiscuous neuregulin receptor signaling, but subsequent lineage progression occurs through a balance of receptor-specific promotion or inhibition of maturation.
Sussman
Caroline R
CR
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4965, USA. caroline.sussman@case.edu
Vartanian
Timothy
T
Miller
Robert H
RH
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004622:Embryo, Mammalian; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009420:Nervous System / Q000166:cytology / Q000196:embryology; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D066247:Receptor, ErbB-4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology
D017931:DNA Primers; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4