title: Neurotrophic factors increase neuregulin expression in embryonic ventral spinal cord neurons.
abstract: Neuregulins (NRGs) are expressed in spinal cord motor neurons and accumulate at the neuromuscular junction where they may increase the synthesis of postsynaptic acetylcholine receptors and voltage-gated sodium channels. We demonstrate here that NRG expression is selectively increased in rat ventral spinal cord neurons at approximately the time that nerve-muscle synapses first form. A rapid increase in NRG mRNA and protein expression was induced in vitro in cultured rat spinal motor neurons by brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, or glial-cell-line-derived neurotrophic factor. Agrin expression was not affected by these factors over the same time course. Brain-derived neurotrophic factor, but not neurotrophin-3, selectively regulated immunoglobulin domain-containing splice variants of NRG, which are likely to be important for binding to the synaptic basal lamina. Regulation of NRG expression in motor neurons by muscle-derived neurotrophic factors may represent one portion of a reciprocal, regulatory loop that promotes neuromuscular synapse development.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Loeb
authors.forename: G D
authors.initials: GD
authors.lastname: Fischbach
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development; D006023:Glycoproteins / Q000378:metabolism*; D007536:Isomerism; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D020880:Neuregulins; D009474:Neurons / Q000378:metabolism*; D020933:Neurotrophin 3; D051381:Rats / Q000196:embryology; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006023:Glycoproteins; D009414:Nerve Growth Factors; D020880:Neuregulins; D020933:Neurotrophin 3