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Friedrich Miescher Institute, P.O. Box 2543, CH-4002 Basel, Switzerland
The characteristic shapes and positions of
each individual body muscle are established during the
process of muscle morphogenesis in response to patterning information from the surrounding mesenchyme. Throughout muscle morphogenesis, primary
myotubes are arranged in small parallel bundles, each
myotube spanning the forming muscles from end to
end. This unique arrangement potentially assigns a crucial role to primary myotube end regions for muscle
morphogenesis.
We have cloned muscle ankyrin repeat protein
(MARP) as a gene induced in adult rat skeletal muscle
by denervation. MARP is the rodent homologue of human C-193 (Chu, W., D.K. Burns, R.A. Swerick, and
D.H. Presky. 1995. J. Biol. Chem. 270:10236-10245) and is identical to rat cardiac ankyrin repeat protein.
(Zou, Y., S. Evans, J. Chen, H.-C. Kuo, R.P. Harvey,
and K.R. Chien. 1997. Development. 124:793-804). In
denervated muscle fibers, MARP transcript accumulated in a unique perisynaptic pattern. MARP was also
expressed in large blood vessels and in cardiac muscle,
where it was further induced by cardiac hypertrophy.
During embryonic development, MARP was expressed
in forming skeletal muscle. In situ hybridization analysis in mouse embryos revealed that MARP transcript
exclusively accumulates at the end regions of primary
myotubes during muscle morphogenesis. This closely coincided with the expression of thrombospondin-4 in
adjacent prospective tendon mesenchyme, suggesting
that these two compartments may constitute a functional unit involved in muscle morphogenesis. Transfection experiments established that MARP protein accumulates in the nucleus and that the levels of both
MARP mRNA and protein are controlled by rapid
degradation mechanisms characteristic of regulatory
early response genes. The results establish the existence
of novel regulatory muscle fiber subcompartments associated with muscle morphogenesis and denervation
and suggest that MARP may be a crucial nuclear cofactor in local signaling pathways from prospective tendon
mesenchyme to forming muscle and from activated
muscle interstitial cells to denervated muscle fibers.
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