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

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

Development ◽

10.1242/dev.125.3.495 ◽

1998 ◽

Vol 125 (3) ◽

pp. 495-505 ◽

Cited By ~ 10

Author(s):

D. Duprez ◽

C. Fournier-Thibault ◽

N. Le Douarin

Keyword(s):

Sonic Hedgehog ◽

Primary Cultures ◽

Posterior Part ◽

Precursor Cells ◽

Limb Bud ◽

Lateral Part ◽

Expression Domain ◽

Muscle Precursor ◽

Muscle Precursor Cells

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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Regulation and Function of SF/HGF during Migration of Limb Muscle Precursor Cells in Chicken

Developmental Biology ◽

10.1006/dbio.1996.0329 ◽

1996 ◽

Vol 180 (2) ◽

pp. 566-578 ◽

Cited By ~ 56

Author(s):

Silke Heymann ◽

Maria Koudrova ◽

H.-H. Arnold ◽

Markus Köster ◽

Thomas Braun

Keyword(s):

Precursor Cells ◽

Limb Muscle ◽

Muscle Precursor ◽

And Function ◽

Muscle Precursor Cells

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Precocious terminal differentiation of premigratory limb muscle precursor cells requires positive signalling

Developmental Dynamics ◽

10.1002/dvdy.20016 ◽

2004 ◽

Vol 229 (3) ◽

pp. 591-599 ◽

Cited By ~ 22

Author(s):

Sara J. Venters ◽

Rebecca E. Argent ◽

Fiona M. Deegan ◽

Gina Perez-Baron ◽

Ted S. Wong ◽

...

Keyword(s):

Terminal Differentiation ◽

Precursor Cells ◽

Limb Muscle ◽

Muscle Precursor ◽

Muscle Precursor Cells

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A highly conserved Wnt-dependent TCF4 binding site within the proximal enhancer of the anti-myogenic Msx1 gene supports expression within Pax3-expressing limb bud muscle precursor cells

Developmental Biology ◽

10.1016/j.ydbio.2007.07.022 ◽

2007 ◽

Vol 311 (2) ◽

pp. 665-678 ◽

Cited By ~ 29

Author(s):

Kerry Ann Miller ◽

John Barrow ◽

J. Martin Collinson ◽

Scott Davidson ◽

Marissa Lear ◽

...

Keyword(s):

Binding Site ◽

Precursor Cells ◽

Limb Bud ◽

Muscle Precursor ◽

Muscle Precursor Cells

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Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity

Genes & Development ◽

10.1101/gad.187807.112 ◽

2012 ◽

Vol 26 (18) ◽

pp. 2103-2117 ◽

Cited By ~ 28

Author(s):

C. Anderson ◽

V. C. Williams ◽

B. Moyon ◽

P. Daubas ◽

S. Tajbakhsh ◽

...

Keyword(s):

Sonic Hedgehog ◽

Precursor Cells ◽

Limb Muscle ◽

Muscle Precursor ◽

Muscle Precursor Cells

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Early specification of limb muscle precursor cells by the homeobox gene Lbx1h

Nature Genetics ◽

10.1038/13843 ◽

1999 ◽

Vol 23 (2) ◽

pp. 213-216 ◽

Cited By ~ 118

Author(s):

Konstanze Schäfer ◽

Thomas Braun

Keyword(s):

Homeobox Gene ◽

Precursor Cells ◽

Limb Muscle ◽

Muscle Precursor ◽

Muscle Precursor Cells

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Distinct signaling molecules control Hoxa-11 and Hoxa-13 expression in the muscle precursor and mesenchyme of the chick limb bud

Development ◽

10.1242/dev.126.12.2771 ◽

1999 ◽

Vol 126 (12) ◽

pp. 2771-2783 ◽

Cited By ~ 1

Author(s):

K. Hashimoto ◽

Y. Yokouchi ◽

M. Yamamoto ◽

A. Kuroiwa

Keyword(s):

Growth Factor ◽

Muscle Development ◽

Hox Genes ◽

Expression Patterns ◽

Precursor Cells ◽

Limb Bud ◽

Posterior Region ◽

Limb Muscle ◽

Limb Mesenchyme ◽

Myogenic Precursor

The limb muscles, originating from the ventrolateral portion of the somites, exhibit position-specific morphological development through successive splitting and growth/differentiation of the muscle masses in a region-specific manner by interacting with the limb mesenchyme and the cartilage elements. The molecular mechanisms that provide positional cues to the muscle precursors are still unknown. We have shown that the expression patterns of Hoxa-11 and Hoxa-13 are correlated with muscle patterning of the limb bud (Yamamoto et al., 1998) and demonstrated that muscular Hox genes are activated by signals from the limb mesenchyme. We dissected the regulatory mechanisms directing the unique expression patterns of Hoxa-11 and Hoxa-13 during limb muscle development. HOXA-11 protein was detected in both the myogenic cells and the zeugopodal mesenchymal cells of the limb bud. The earlier expression of HOXA-11 in both the myogenic precursor cells and the mesenchyme was dependent on the apical ectodermal ridge (AER), but later expression was independent of the AER. HOXA-11 expression in both myogenic precursor cells and mesenchyme was induced by fibroblast growth factor (FGF) signal, whereas hepatocyte growth factor/scatter factor (HGF/SF) maintained HOXA-11 expression in the myogenic precursor cells, but not in the mesenchyme. The distribution of HOXA-13 protein expression in the muscle masses was restricted to the posterior region. We found that HOXA-13 expression in the autopodal mesenchyme was dependent on the AER but not on the polarizing region, whereas expression of HOXA-13 in the posterior muscle masses was dependent on the polarizing region but not on the AER. Administration of BMP-2 at the anterior margin of the limb bud induced ectopic HOXA-13 expression in the anterior region of the muscle masses followed by ectopic muscle formation close to the source of exogenous BMP-2. In addition, NOGGIN/CHORDIN, antagonists of BMP-2 and BMP-4, downregulated the expression of HOXA-13 in the posterior region of the muscle masses and inhibited posterior muscle development. These results suggested that HOXA-13 expression in the posterior muscle masses is activated by the posteriorizing signal from the posterior mesenchyme via BMP-2. On the contrary, the expression of HOXA-13 in the autopodal mesenchyme was affected by neither BMP-2 nor NOGGIN/CHORDIN. Thus, mesenchymal HOXA-13 expression was independent of BMP-2 from polarizing region, but was under the control of as yet unidentified signals from the AER. These results showed that expression of Hox genes is regulated differently in the limb muscle precursor and mesenchymal cells.

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