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Insulin‐like growth factor I stimulates myoblast expansion and myofiber development in the limb
Author(s) -
Mitchell Pamela J.,
Johnson Sally E.,
Han Kevin
Publication year - 2002
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.1227
Subject(s) - biology , myocyte , insulin like growth factor , endocrinology , hyperplasia , medicine , muscle hypertrophy , myogenesis , hindlimb , anatomy , growth factor , population , limb development , embryo , microbiology and biotechnology , receptor , biochemistry , environmental health
Insulin‐like growth factor I (IGF‐I) is expressed in the anterior and posterior mesodermal cells of the developing limb. However, a definite role for IGF‐I during early limb organogenesis is unknown. To determine the inherent participation of IGF‐I during limb organ development, a retroviral delivery system (RCAS) was used to overexpress IGF‐I throughout the developing hind limb of stage 24 chicken embryos. The area of the belly of the external gastrocnemius muscle in the IGF‐I infected limb was an average of 160, 90, 70, and 80% larger than the contralateral control muscle belly, 4, 5, 6, and 7 days postinjection, respectively (all differences P < 0.01). In comparison to the contralateral control muscles, there were a significantly greater number of muscle fibers in the IGF‐I infected muscles ( P < 0.05), confirming that the majority of IGF‐I–mediated muscle enlargement was due to an increase in total fiber numbers (hyperplasia). Four days postinjection, there was a 32% increase in myoblast to myofiber ratio in the muscle of injected limbs compared with the muscle in the contralateral noninjected control limbs ( P < 0.05). This result demonstrates that IGF‐I acts to expand the undifferentiated myoblast population, and as a result, more myofibers subsequently develop, and the muscles expressing ectopic IGF‐I are enlarged by means of hyperplasia. There was no difference in tibiotarsus and fibula length or diameter between the IGF‐I injected and control limb, suggesting that ectopic IGF‐I expression within the mesoderm was not a nonspecific growth stimulant of all tissues of the developing limb, but specifically enhanced skeletal muscle development and growth. Ectopic IGF‐I expression had no significant effect on myostatin mRNA concentrations. Our results support a model where mesodermally expressed IGF‐I acts to regulate the number of primary myofibers, and, therefore, size of skeletal muscles, which form during the initial events of limb myogenesis. © 2001 Wiley‐Liss, Inc.