Sonic Hedgehog induces proliferation of committed skeletal muscle cells in the chick limb

Myogenic Regulatory Factors (MRFs) are a family of transcription factors whose expression in a cell reflects the commitment of this cell to a myogenic fate before any cytological sign of muscle differentiation is detectable. Myogenic cells in limb skeletal muscles originate from the lateral half of the somites. Cells that migrate away from the lateral part of the somites to the limb bud do not initially express any member of the MRF family. Expression of MRFs in the muscle precursor cells starts after the migration process is completed. The extracellular signals involved in activating the myogenic programme in muscle precursor cells in the limb in vivo are not known. We wished to investigate whether Sonic Hedgehog (SHH) expressed in the posterior part of the limb bud could be involved in differentiation of the muscle precursor cells in the limb. We found that retrovirally overexpressed SHH in the limb bud induced the extension of the expression domain of the Pax-3 gene, then that of the MyoD gene and finally that of the myosin protein. This led to an hypertrophy of the muscles in vivo. Addition of SHH to primary cultures of myoblasts resulted in an increase in the proportion of myoblasts that incorporate bromodeoxyuridine, resulting in an increase of myotube number. These data show that SHH is able to activate myogenesis in vivo and in vitro in already committed myoblasts and suggest that the stimulation of the myogenic programme by SHH involves activation of cell proliferation.

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Coordinated expression of Hoxa-11 and Hoxa-13 during limb muscle patterning

Development ◽

10.1242/dev.125.7.1325 ◽

1998 ◽

Vol 125 (7) ◽

pp. 1325-1335 ◽

Cited By ~ 1

Author(s):

M. Yamamoto ◽

Y. Gotoh ◽

K. Tamura ◽

M. Tanaka ◽

A. Kawakami ◽

...

Keyword(s):

Hox Genes ◽

Anterior Part ◽

Posterior Part ◽

Precursor Cells ◽

Limb Bud ◽

Limb Muscle ◽

Limb Buds ◽

Muscle Precursor ◽

Muscle Precursor Cells ◽

Ventral Muscle

The limb muscle precursor cells migrate from the somites and congregate into the dorsal and ventral muscle masses in the limb bud. Complex muscle patterns are formed by successive splitting of the muscle masses and subsequent growth and differentiation in a region-specific manner. Hox genes, known as key regulator genes of cartilage pattern formation in the limb bud, were found to be expressed in the limb muscle precursor cells. We found that HOXA-11 protein was expressed in the premyoblasts in the limb bud, but not in the somitic cells or migrating premyogenic cells in the trunk at stage 18. By stage 24, HOXA-11 expression began to decrease from the posterior halves of the muscle masses. HOXA-13 was expressed strongly in the myoblasts of the posterior part in the dorsal/ventral muscle masses and weakly in a few myoblasts of the anterior part of the dorsal muscle mass. Transplantation of the lateral plate of the presumptive wing bud to the flank induced migration of premyoblasts from somites to the graft. Under these conditions, HOXA-11 expression was induced in the migrating premyoblasts in the ectopic limb buds. Application of retinoic acid at the anterior margin of the limb bud causes duplication of the autopodal cartilage and transformation of the radius to the ulna, and at the same time induces duplication of the muscle pattern along the anteroposterior axis. Under these conditions, HOXA-13 was also induced in the anterior region of the ventral muscles in the zeugopod. These results suggest that Hoxa-11 and Hoxa-13 expression in the migrating premyoblasts is under the control of the limb mesenchyme and the polarizing signal(s). In addition, these results indicate that these Hox genes are involved in muscle patterning in the limb buds.

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