Neu differentiation factor is a neuron-glia signal and regulates survival, proliferation, and maturation of rat Schwann cell precursors.
We show that beta forms of Neu differentiation factor (NDF), homologous to acetylcholine receptor-inducing activity, glial growth factor, and heregulin, prevent apoptotic death and stimulate DNA synthesis of the E14 Schwann cell precursor, an early cell in the rat Schwann cell lineage. When precursors are exposed to NDF in defined medium, they generate Schwann cells without the requirement for DNA synthesis and with a time course that is similar to that with which Schwann cells appear in embryonic nerves in vivo. Furthermore, a neuronal signal that also mediates precursor survival and maturation is blocked by the extracellular domain of the ErbB4 NDF receptor, a protein that specifically blocks the action of NDFs. These observations provide important evidence that NDF is one of the hitherto elusive neuron-glia signaling molecules long proposed to regulate development in the Schwann cell lineage.
Dong
Z
Z
Department of Anatomy and Developmental Biology, University College London, England.
Brennan
A
A
Liu
N
N
Yarden
Y
Y
Lefkowitz
G
G
Mirsky
R
R
Jessen
K R
KR
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D066246:ErbB Receptors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology; D020880:Neuregulins; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D066247:Receptor, ErbB-4; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D003470:Culture Media; D006023:Glycoproteins; D020880:Neuregulins; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D004247:DNA; D066246:ErbB Receptors; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4