Neuregulin for muscle spindle fiber

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Research Abstract from Proc Natl Acad Sci U S A. 2004 Aug 9

Neuregulin induces the expression of transcription factors and myosin

heavy chains typical of muscle spindles in cultured human muscle.

son C, Duggan D, Fischbach G.

Microarray Unit, Genetics and Genomics Section, National Institute of

Arthritis and Musculoskeletal and Skin Diseases, National Institutes of

Health, Bethesda, MD 20892; Translational Genomics Research Institute

(TGen), Phoenix, AZ 85004.

Neuregulin (NRG) (also known as ARIA, GGF, and other names) is a heparin

sulfate proteoglycan secreted into the neuromuscular junction by

innervating motor and sensory neurons. An integral part of synapse

formation, we have analyzed NRG-induced changes in gene expression over

48 h in primary human myotubes. We show that in addition to increasing

the expression of acetylcholine receptors on the myotube surface, NRG

treatment results in a transient increase of several members of the

early growth response (Egr) family of transcription factors. Three Egrs,

Egr1, -2, and -3, are induced within the first hour of NRG treatment,

with Egr1 and -3 RNA levels showing the most significant increases of

approximately 9- and 16-fold, respectively. Also noted was a

corresponding increase in protein levels for both of these transcription

factors. Previous literature indicates that Egr3 expression is required

for the formation of muscle spindle fibers, sensory organs that are

distinct from skeletal muscle contractile fibers. At the molecular

level, muscle spindle fibers express a unique subset of myosin heavy

chains. Two isoforms of the myosin heavy chain, the slow development and

neonatal, were found to be increased in our myotube cultures after 48 h

of treatment with NRG. Taken together, these results indicate that not

only can NRG induce the expression of a transcription factor key to

spindle fiber development (Egr3), but that a portion of this

developmental process can be replicated in vitro.