Sonic hedgehog enhances somite cell viability and formation of primary slow muscle fibers in avian segmented mesoderm |
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Authors: | Gordon M Cann Jay W Lee and F E Stockdale |
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Institution: | (1) Department of Medicine, Stanford University, Stanford, CA 94305-5115, USA e-mail: mlfes@leland.stanford.edu, Tel.: 650-725-6449, Fax: +1-650-725-1420, US |
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Abstract: | Primary skeletal muscle fibers first form in the segmented portions of paraxial mesoderm called somites. Although the neural
tube and notochord are recognized as crucial in patterning myogenic cell lineages during avian and mammalian somitic myogenesis,
the source, identities, and actions of the signals governing this process remain controversial. It has been shown that signals
emanating from the ventral neural tube and/or notochord alone or Shh alone serve to activate MyoD expression in somites. However, beyond a role in initiating MyoD expression, little is known about the effects of Shh on primary muscle fiber formation in somites of higher vertebrates.
The studies reported here investigate how the ventral neural tube promotes myogenesis and compare the effects of the ventral
neural tube with those of purified Shh protein on fiber formation in somites. We show that purified Shh protein mimics actions
of the ventral neural tube on somites including initiation of muscle fiber formation, enhancement of numbers of primary muscle
fibers, and particularly, the formation of primary fibers that express slow myosin. There is a marked increase in slow myosin
expression in fibers in response to Shh as somites mature. The effects of ventral neural tube on fiber formation can be blocked
by disrupting the Shh signaling pathway by increasing the activity of somitic cyclic AMP-dependent protein kinase A. Furthermore,
it was demonstrated that apoptosis is a dominant fate of somite cells, but not somitic muscle fibers, when cultured in the
absence of the neural tube, and that application of Shh protein to somites reduced apoptosis. The block to apoptosis by Shh
is a manifestation of the maturity of the somite with a progressive increase in the block as somites are displaced rostrally
from somite III forward. We conclude that purified Shh protein in mimicking the effects of the ventral neural tube on segmented
mesoderm can exert pleiotropic effects during primary myogenesis, including: control of the proliferative expansion of myogenic
progenitor cells, antagonism of cell death pathways within the precursors to muscle fibers, and during the crucial process
of primary myogenesis, can exert an effect on diversification of muscle fiber types.
Accepted: 1 March 1999 |
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Keywords: | Somite explant culture Sonic hedgehog protein Myogenic induction Primary fiber type diversity Apoptosis |
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