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

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4885-4893 ◽  
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.

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

Development ◽  
1999 ◽  
Vol 126 (12) ◽  
pp. 2771-2783 ◽  
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.

Retinoic acid signaling is required during early chick limb development

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1385-1394 ◽  
Author(s):  
J.A. Helms ◽  
C.H. Kim ◽  
G. Eichele ◽  
C. Thaller
Keyword(s):  
Retinoic Acid ◽  
Limb Development ◽  
Acid Synthesis ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Retinoid Receptor ◽  
Limb Morphogenesis ◽  
Wing Bud ◽  
Zone Of Polarizing Activity

In the chick limb bud, the zone of polarizing activity controls limb patterning along the anteroposterior and proximodistal axes. Since retinoic acid can induce ectopic polarizing activity, we examined whether this molecule plays a role in the establishment of the endogenous zone of polarizing activity. Grafts of wing bud mesenchyme treated with physiologic doses of retinoic acid had weak polarizing activity but inclusion of a retinoic acid-exposed apical ectodermal ridge or of prospective wing bud ectoderm evoked strong polarizing activity. Likewise, polarizing activity of prospective wing mesenchyme was markedly enhanced by co-grafting either a retinoic acid-exposed apical ectodermal ridge or ectoderm from the wing region. This equivalence of ectoderm-mesenchyme interactions required for the establishment of polarizing activity in retinoic acid-treated wing buds and in prospective wing tissue, suggests a role of retinoic acid in the establishment of the zone of polarizing activity. We found that prospective wing bud tissue is a high-point of retinoic acid synthesis. Furthermore, retinoid receptor-specific antagonists blocked limb morphogenesis and down-regulated a polarizing signal, sonic hedgehog. Limb agenesis was reversed when antagonist-exposed wing buds were treated with retinoic acid. Our results demonstrate a role of retinoic acid in the establishment of the endogenous zone of polarizing activity.

The role of Lbx1 in migration of muscle precursor cells

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 437-445 ◽  
Author(s):  
H. Brohmann ◽  
K. Jagla ◽  
C. Birchmeier
Keyword(s):  
Homeobox Gene ◽  
Branchial Arch ◽  
Precursor Cells ◽  
Muscle Precursor ◽  
Hindlimb Muscles ◽  
Expression Of Genes ◽  
Extensor Muscles ◽  
Septum Transversum ◽  
Muscle Precursor Cells

The homeobox gene Lbx1 is expressed in migrating hypaxial muscle precursor cells during development. These precursors delaminate from the lateral edge of the dermomyotome and form distinct streams that migrate over large distances, using characteristic paths. The targets of migration are limbs, septum transversum and the floor of the first branchial arch where the cells form skeletal muscle of limbs and shoulders, diaphragm and hypoglossal cord, respectively. We used gene targeting to analyse the function of Lbx1 in the mouse. Myogenic precursor cells delaminate from the dermomyotome in Lbx1 mutants, but migrate in an aberrant manner. Most critically affected are migrating cells that move to the limbs. Precursor cells that reach the dorsal limb field are absent. In the ventral limb, precursors are present but distributed in an abnormal manner. As a consequence, at birth some muscles in the forelimbs are completely lacking (extensor muscles) or reduced in size (flexor muscles). Hindlimb muscles are affected strongly, and distal limb muscles are more affected than proximal ones. Other migrating precursor cells heading towards the floor of the first branchial arch move along the appropriate path in Lbx1 mutants. However, these cells migrate less efficiently and reduced numbers of precursors reach their distal target. At birth, the internal lingual muscle is therefore reduced in size. We suggest that Lbx1 controls the expression of genes that are essential for the recognition or interpretation of cues that guide migrating muscle precursors and maintain their migratory potential.

rolling pebbles(rols) is required inDrosophilamuscle precursors for recruitment of myoblasts for fusion

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 5061-5073 ◽  
Author(s):  
Annette Rau ◽  
Detlev Buttgereit ◽  
Anne Holz ◽  
Richard Fetter ◽  
Stephen K. Doberstein ◽  
...  
Keyword(s):  
Amino Acids ◽  
Transcription Initiation ◽  
Muscle Development ◽  
Precursor Cells ◽  
Malpighian Tubules ◽  
Muscle Precursor ◽  
Terminal Amino ◽  
Founder Cells ◽  
Fusion Competent Myoblasts ◽  
Muscle Precursor Cells

Mutations in the rolling pebbles (rols) gene result in severe defects in myoblast fusion. Muscle precursor cells are correctly determined, but myogenesis does not progress significantly beyond this point because recognition and/or cell adhesion between muscle precursor cells and fusion-competent myoblasts is disturbed. Molecular analysis of the rols genomic region reveals two variant transcripts of rols due to different transcription initiation sites, rols6 and rols7. rols6 mRNA is detectable mainly in the endoderm during differentiation as well as in malpighian tubules and in the epidermis. By contrast, rols7 expression is restricted to the mesoderm and later to progenitor descendants during somatic and pharyngeal muscle development. Transcription starts at the extended germ band stage when progenitor/founder cells are determined and persists until stage 13. The proteins encoded by the rols gene are 1670 (Rols6) and 1900 (Rols7) amino acids in length. Both forms contain an N-terminal RING-finger motif, nine ankyrin repeats and a TPR repeat eventually overlaid by a coiled-coil domain. The longer protein, Rols7, is characterized by 309 unique N-terminal amino acids, while Rols6 is distinguishable by 79 N-terminal amino acids. Expression of rols7 in muscle founder cells indicates a function of Rols7 in these cells. Transplantation assays of rols mutant mesodermal cells into wild-type embryos show that Rols is required in muscle precursor cells and is essential to recruit fusion-competent myoblasts for myotube formation.

Analysis of the callipyge phenotype through skeletal muscle development; association of Dlk1 with muscle precursor cells

2008 ◽  
Vol 76 (3) ◽  
pp. 283-298 ◽  
Author(s):  
Jason D. White ◽  
Tony Vuocolo ◽  
Matthew McDonagh ◽  
Miranda D. Grounds ◽  
Gregory S. Harper ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Precursor Cells ◽  
Skeletal Muscle Development ◽  
Muscle Precursor ◽  
Muscle Precursor Cells

scholarly journals Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Wang ◽  
Lin Xu ◽  
Jiro Miura ◽  
Mithun Kumar Saha ◽  
Yume Uemura ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Muscle Development ◽  
Branchial Arch ◽  
Precursor Cells ◽  
Cellular Mechanisms ◽  
Pregnant Mice ◽  
Cranial Neural Crest Cells ◽  
Cranial Muscle

The first and second branchiomeric (branchial arch) muscles are craniofacial muscles that derive from branchial arch mesoderm. In mammals, this set of muscles is indispensable for jaw movement and facial expression. Defects during embryonic development that result in congenital partial absence of these muscles can have significant impact on patients’ quality of life. However, the detailed molecular and cellular mechanisms that regulate branchiomeric muscle development remains poorly understood. Herein we investigated the role of retinoic acid (RA) signaling in developing branchiomeric muscles using mice as a model. We administered all-trans RA (25 mg/kg body weight) to Institute of Cancer Research (ICR) pregnant mice by gastric intubation from E8.5 to E10.5. In their embryos at E13.5, we found that muscles derived from the first branchial arch (temporalis, masseter) and second branchial arch (frontalis, orbicularis oculi) were severely affected or undetectable, while other craniofacial muscles were hypoplastic. We detected elevated cell death in the branchial arch mesoderm cells in RA-treated embryos, suggesting that excessive RA signaling reduces the survival of precursor cells of branchiomeric muscles, resulting in the development of hypoplastic craniofacial muscles. In order to uncover the signaling pathway(s) underlying this etiology, we focused on Pitx2, Tbx1, and MyoD1, which are critical for cranial muscle development. Noticeably reduced expression of all these genes was detected in the first and second branchial arch of RA-treated embryos. Moreover, elevated RA signaling resulted in a reduction in Dlx5 and Dlx6 expression in cranial neural crest cells (CNCCs), which disturbed their interactions with branchiomeric mesoderm cells. Altogether, we discovered that embryonic craniofacial muscle defects caused by excessive RA signaling were associated with the downregulation of Pitx2, Tbx1, MyoD1, and Dlx5/6, and reduced survival of cranial myogenic precursor cells.

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

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 495-505 ◽  
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.

Evidence that preaxial polydactyly in the Doublefoot mutant is due to ectopic Indian Hedgehog signaling

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3123-3132 ◽  
Author(s):  
Y. Yang ◽  
P. Guillot ◽  
Y. Boyd ◽  
M.F. Lyon ◽  
A.P. McMahon
Keyword(s):  
Hedgehog Signaling ◽  
Interspecific Backcross ◽  
Limb Bud ◽  
Chromosome 1 ◽  
Indian Hedgehog ◽  
Posterior Limb ◽  
Preaxial Polydactyly ◽  
Ectopic Activation ◽  
Zone Of Polarizing Activity ◽  
Anterior Posterior

Patterning of the vertebrate limb along the anterior-posterior axis is controlled by the zone of polarizing activity (ZPA) located at the posterior limb margin. One of the vertebrate Hh family members, Shh, has been shown to be able to mediate the function of the ZPA. Several naturally occurring mouse mutations with the phenotype of preaxial polydactyly exhibit ectopic Shh expression at the anterior limb margin. In this study, we report the molecular characterization of a spontaneous mouse mutation, Doublefoot (Dbf). Dbf is a dominant mutation which maps to chromosome 1. Heterozygous and homozygous embryos display a severe polydactyly with 6 to 8 digits on each limb. We show here that Shh is expressed normally in Dbf mutants. In contrast, a second Hh family member, Indian hedgehog (Ihh) which maps close to Dbf, is ectopically expressed in the distal limb bud. Ectopic Ihh expression in the distal and anterior limb bud results in the ectopic activation of several genes associated with anterior-posterior and proximal-distal patterning (Fgf4, Hoxd13, Bmp2). In addition, specific components in the Hedgehog pathway are either ectopically activated (Ptc, Ptc-2, Gli1) or repressed (Gli2). We propose that misexpression of Ihh, and not a novel Smoothened ligand as recently suggested (Hayes et al., 1998), is responsible for the Dbf phenotype. We consider that Ihh has a similar activity to Shh when expressed in the early Shh-responsive limb bud. To determine whether Dbf maps to the Ihh locus, which is also on chromosome 1, we performed an interspecific backcross. These results demonstrate that Dbf and Ihh are genetically separated by approximately 1.3 centimorgans, suggesting that Dbf mutation may cause an exceptionally long-range disruption of Ihh regulation. Although this leads to ectopic activation of Ihh, normal expression of Ihh in the cartilaginous elements is retained.

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