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Volume 17, Number 4, Issue of February 15, 1997 pp. 1416-1424
Copyright ©1997 Society for Neuroscience

Neurotrophic Factors Increase Neuregulin Expression in Embryonic Ventral Spinal Cord Neurons

Received Sept. 24, 1996; revised Dec. 2, 1996; accepted Dec. 5, 1996.

Jeffrey A. Loeb and Gerald D. Fischbach

Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115

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.

Key words: ARIA; neuregulin; neurotrophin; motor neuron; agrin; GDNF; BDNF; NT-3; NT-4

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