Development, Vol 126, Issue 4 781-791, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

Expression patterns of transmembrane and released forms of neuregulin during spinal cord and neuromuscular synapse development

JA Loeb, TS Khurana, JT Robbins, AG Yee and GD Fischbach
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. jloeb@med.wayne.edu

We mapped the distribution of neuregulin and its transmembrane precursor in developing, embryonic chick and mouse spinal cord. Neuregulin mRNA and protein were expressed in motor and sensory neurons shortly after their birth and levels steadily increased during development. Expression of the neuregulin precursor was highest in motor and sensory neuron cell bodies and axons, while soluble, released neuregulin accumulated along early motor and sensory axons, radial glia, spinal axonal tracts and neuroepithelial cells through associations with heparan sulfate proteoglycans. Neuregulin accumulation in the synaptic basal lamina of neuromuscular junctions occurred significantly later, coincident with a reorganization of muscle extracellular matrix resulting in a relative concentration of heparan sulfate proteoglycans at endplates. These results demonstrate an early axonal presence of neuregulin and its transmembrane precursor at developing synapses and a role for heparan sulfate proteoglycans in regulating the temporal and spatial sites of soluble neuregulin accumulation during development.

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