Characterization of migration behavior of myogenic precursor cells in the limb bud with respect to Lmx1b expression

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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Isolation and characterization of myogenic precursor cells from human cremaster muscle

Scientific Reports ◽

10.1038/s41598-019-40042-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Neia Naldaiz-Gastesi ◽

María Goicoechea ◽

Isabel M-ª Aragón ◽

Virginia Pérez-López ◽

Sandra Fuertes-Alvarez ◽

...

Keyword(s):

Precursor Cells ◽

Cremaster Muscle ◽

Isolation And Characterization ◽

Myogenic Precursor

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SF/HGF is a mediator between limb patterning and muscle development

Development ◽

10.1242/dev.126.21.4885 ◽

1999 ◽

Vol 126 (21) ◽

pp. 4885-4893 ◽

Cited By ~ 3

Author(s):

M. Scaal ◽

A. Bonafede ◽

V. Dathe ◽

M. Sachs ◽

G. Cann ◽

...

Keyword(s):

Muscle Development ◽

Precursor Cells ◽

Limb Bud ◽

Posterior Limb ◽

Undifferentiated State ◽

Direction Control ◽

Zone Of Polarizing Activity ◽

Muscle Precursor Cells ◽

Myogenic Precursor

Scatter factor/hepatocyte growth factor (SF/HGF) is known to be involved in the detachment of myogenic precursor cells from the lateral dermomyotomes and their subsequent migration into the newly formed limb buds. As yet, however, nothing has been known about the role of the persistent expression of SF/HGF in the limb bud mesenchyme during later stages of limb bud development. To test for a potential role of SF/HGF in early limb muscle patterning, we examined the regulation of SF/HGF expression in the limb bud as well as the influence of SF/HGF on direction control of myogenic precursor cells in limb bud mesenchyme. We demonstrate that SF/HGF expression is controlled by signals involved in limb bud patterning. In the absence of an apical ectodermal ridge (AER), no expression of SF/HGF in the limb bud is observed. However, FGF-2 application can rescue SF/HGF expression. Excision of the zone of polarizing activity (ZPA) results in ectopic and enhanced SF/HGF expression in the posterior limb bud mesenchyme. We could identify BMP-2 as a potential inhibitor of SF/HGF expression in the posterior limb bud mesenchyme. We further demonstrate that ZPA excision results in a shift of Pax-3-positive cells towards the posterior limb bud mesenchyme, indicating a role of the ZPA in positioning of the premuscle masses. Moreover, we present evidence that, in the limb bud mesenchyme, SF/HGF increases the motility of myogenic precursor cells and has a role in maintaining their undifferentiated state during migration. We present a model for a crucial role of SF/HGF during migration and early patterning of muscle precursor cells in the vertebrate limb.

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Mapping of myogenin transcription during embryogenesis using transgenes linked to the myogenin control region.

The Journal of Cell Biology ◽

10.1083/jcb.119.6.1649 ◽

1992 ◽

Vol 119 (6) ◽

pp. 1649-1656 ◽

Cited By ~ 44

Author(s):

T C Cheng ◽

T A Hanley ◽

J Mudd ◽

J P Merlie ◽

E N Olson

Keyword(s):

Dna Sequences ◽

Precursor Cells ◽

Fiber Formation ◽

Limb Bud ◽

Embryonic Cells ◽

Cis Acting ◽

Helix Loop Helix ◽

Myogenic Lineage ◽

Flanking Region ◽

Myogenic Precursor

During vertebrate embryogenesis, the muscle-specific helix-loop-helix protein myogenin is expressed in muscle cell precursors in the developing somite myotome and limb bud before muscle fiber formation and is further upregulated during myogenesis. We show that cis-acting DNA sequences within the 5' flanking region of the mouse myogenin gene are sufficient to direct appropriate temporal, spatial, and tissue-specific transcription of myogenin during mouse embryogenesis. Myogenin-lacZ transgenes trace the fate of embryonic cells that activate myogenin transcription and suggest that myogenic precursor cells that migrate from the somite myotome to the limb bud are committed to a myogenic fate in the absence of myogenin transcription. Activation of a myogenin-lacZ transgene can occur in limb bud explants in culture, indicating that signals required for activation of myogenin transcription are intrinsic to the limb bud and independent of other parts of the embryo. These results reveal multiple populations of myogenic precursor cells during development and suggest the existence of regulators other than myogenic helix-loop-helix proteins that maintain cells in the early limb bud in the myogenic lineage.

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Culture, identification and characterization of rat oligodendrocyte precursor cells in vitro

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2012.00130 ◽

2012 ◽

Vol 32 (2) ◽

pp. 130-135

Author(s):

Mei-lan CHEN ◽

Zhong-jun TANG ◽

Jian MING ◽

Hao WANG ◽

Chun HU ◽

...

Keyword(s):

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Oligodendrocyte Precursor ◽

Culture Identification ◽

Identification And Characterization

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Characterization of Cre Recombinase Activity for In Vivo Targeting of Adipocyte Precursor Cells

Stem Cell Reports ◽

10.1016/j.stemcr.2014.10.009 ◽

2014 ◽

Vol 3 (6) ◽

pp. 1147-1158 ◽

Cited By ~ 57

Author(s):

Katherine C. Krueger ◽

Maria José Costa ◽

Hongqing Du ◽

Brian J. Feldman

Keyword(s):

Cre Recombinase ◽

Precursor Cells ◽

Adipocyte Precursor

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MyoD and Myf-5 define the specification of musculature of distinct embryonic origin

Biochemistry and Cell Biology ◽

10.1139/o98-107 ◽

1998 ◽

Vol 76 (6) ◽

pp. 1079-1091 ◽

Cited By ~ 44

Author(s):

Boris Kablar ◽

Atsushi Asakura ◽

Kirsten Krastel ◽

Chuyan Ying ◽

Linda L May ◽

...

Keyword(s):

Abdominal Wall ◽

Expression Pattern ◽

Branchial Arch ◽

Precursor Cells ◽

Mouse Development ◽

Unique Role ◽

Branchial Arches ◽

Embryonic Origin ◽

Body Wall Muscles ◽

Myogenic Precursor

Mounting evidence supports the notion that Myf-5 and MyoD play unique roles in the development of epaxial (originating in the dorso-medial half of the somite, e.g. back muscles) and hypaxial (originating in the ventro-lateral half of the somite, e.g. limb and body wall muscles) musculature. To further understand how Myf-5 and MyoD genes co-operate during skeletal muscle specification, we examined and compared the expression pattern of MyoD-lacZ (258/-2.5lacZ and MD6.0-lacZ) transgenes in wild-type, Myf-5, and MyoD mutant embryos. We found that the delayed onset of muscle differentiation in the branchial arches, tongue, limbs, and diaphragm of MyoD-/- embryos was a consequence of a reduced ability of myogenic precursor cells to progress through their normal developmental program and not because of a defect in migration of muscle progenitor cells into these regions. We also found that myogenic precursor cells for back, intercostal, and abdominal wall musculature in Myf-5-/-embryos failed to undergo normal translocation or differentiation. By contrast, the myogenic precursors of intercostal and abdominal wall musculature in MyoD-/- embryos underwent normal translocation but failed to undergo timely differentiation. In conclusion, these observations strongly support the hypothesis that Myf-5 plays a unique role in the development of muscles arising after translocation of epithelial dermamyotome cells along the medial edge of the somite to the subjacent myotome (e.g., back or epaxial muscle) and that MyoD plays a unique role in the development of muscles arising from migratory precursor cells (e.g., limb and branchial arch muscles, tongue, and diaphragm). In addition, the expression pattern of MyoD-lacZ transgenes in the intercostal and abdominal wall muscles of Myf-5-/- and MyoD-/- embryos suggests that appropriate development of these muscles is dependent on both genes and, therefore, these muscles have a dual embryonic origin (epaxial and hypaxial).Key words: epaxial and hypaxial muscle, Myf-5, MyoD, mouse development, somite.

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Involvement of RBP-J in biological functions of mouse Notch1 and its derivatives

Development ◽

10.1242/dev.124.20.4133 ◽

1997 ◽

Vol 124 (20) ◽

pp. 4133-4141 ◽

Cited By ~ 15

Author(s):

H. Kato ◽

Y. Taniguchi ◽

H. Kurooka ◽

S. Minoguchi ◽

T. Sakai ◽

...

Keyword(s):

Cell Fate ◽

Mutant Cell ◽

Precursor Cells ◽

Physical Interaction ◽

Binding Motifs ◽

Cell Lineages ◽

Transactivation Activity ◽

Vp16 Fusion ◽

Myogenic Precursor

Notch is involved in the cell fate determination of many cell lineages. The intracellular region (RAMIC) of Notch1 transactivates genes by interaction with a DNA binding protein RBP-J. We have compared the activities of mouse RAMIC and its derivatives in transactivation and differentiation suppression of myogenic precursor cells. RAMIC comprises two separate domains, IC for transactivation and RAM for RBP-J binding. Although the physical interaction of IC with RBP-J was much weaker than with RAM, transactivation activity of IC was shown to involve RBP-J by using an RBP-J null mutant cell line. IC showed differentiation suppression activity that was generally comparable to its transactivation activity. The RBP-J-VP16 fusion protein, which has strong transactivation activity, also suppressed myogenesis of C2C12. The RAM domain, which has no other activities than binding to RBP-J, synergistically stimulated transactivation activity of IC to the level of RAMIC. The RAM domain was proposed to compete with a putative co-repressor for binding to RBP-J because the RAM domain can also stimulate the activity of RBP-J-VP16. These results taken together, indicate that differentiation suppression of myogenic precursor cells by Notch signalling is due to transactivation of genes carrying RBP-J binding motifs.

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Differentiation of Human Embryonic Stem Cells into Engrafting Myogenic Precursor Cells

Stem Cells Research and Therapeutics International ◽

10.31579/2643-1912/002 ◽

2019 ◽

Vol 1 (1) ◽

pp. 01-05

Author(s):

Stalin Reddy Challa ◽

Swathi Goli

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Precursor Cells ◽

Functional Improvement ◽

Serum Free ◽

Myogenic Stem Cells ◽

Serum Free Conditions ◽

Myogenic Precursor

Degenerative muscle diseases affect muscle tissue integrity and function. Human embryonic stem cells (hESC) are an attractive source of cells to use in regenerative therapies due to their unlimited capacity to divide and ability to specialize into a wide variety of cell types. A practical way to derive therapeutic myogenic stem cells from hESC is lacking. In this study, we demonstrate the development of two serum-free conditions to direct the differentiation of hESC towards a myogenic precursor state. Using TGFß and PI3Kinase inhibitors in combination with bFGF we showed that one week of differentiation is sufficient for hESC to specialize into PAX3+/PAX7+ myogenic precursor cells. These cells also possess the capacity to further differentiate in vitro into more specialized myogenic cells that express MYOD, Myogenin, Desmin and MYHC, and showed engraftment in vivo upon transplantation in immunodeficient mice. Ex vivo myomechanical studies of dystrophic mouse hindlimb muscle showed functional improvement one month post-transplantation. In summary, this study describes a promising system to derive engrafting muscle precursor cells solely using chemical substances in serum-free conditions and without genetic manipulation.

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