scholarly journals BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jaeyoung Shin ◽  
Shuichi Watanabe ◽  
Soraya Hoelper ◽  
Marcus Krüger ◽  
Sawa Kostin ◽  
...  

Migration of skeletal muscle precursor cells is a key step during limb muscle development and depends on the activity of PAX3 and MET. Here, we demonstrate that BRAF serves a crucial function in formation of limb skeletal muscles during mouse embryogenesis downstream of MET and acts as a potent inducer of myoblast cell migration. We found that a fraction of BRAF accumulates in the nucleus after activation and endosomal transport to a perinuclear position. Mass spectrometry based screening for potential interaction partners revealed that BRAF interacts and phosphorylates PAX3. Mutation of BRAF dependent phosphorylation sites in PAX3 impaired the ability of PAX3 to promote migration of C2C12 myoblasts indicating that BRAF directly activates PAX3. Since PAX3 stimulates transcription of the Met gene we propose that MET signaling via BRAF fuels a positive feedback loop, which maintains high levels of PAX3 and MET activity required for limb muscle precursor cell migration.

Development ◽  
2001 ◽  
Vol 128 (23) ◽  
pp. 4669-4680 ◽  
Author(s):  
Mary E. Swartz ◽  
Johann Eberhart ◽  
Elena B. Pasquale ◽  
Catherine E. Krull

Limb muscles derive from muscle precursor cells that lie initially in the lateral portion of the somitic dermomyotome and subsequently migrate to their target limb regions, where muscle-specific gene transcription is initiated. Although several molecules that control the generation and delamination of muscle precursor cells have been identified, little is known about the mechanisms that guide muscle precursor cell migration in the limb. We have examined the distribution of members of the Eph family during muscle precursor cell development. The EphA4 receptor tyrosine kinase and its ligand, ephrin-A5, are expressed by muscle precursor cells and forelimb mesoderm in unique spatiotemporal patterns during the period when muscle precursors delaminate from the dermomyotome and migrate into the limb. To test the function of EphA4/ephrin-A5 interactions in muscle precursor migration, we used targeted in ovo electroporation to express ephrin-A5 ectopically specifically in the presumptive limb mesoderm. In the presence of ectopic ephrin-A5, Pax7-positive muscle precursor cells are significantly reduced in number in the proximal limb, compared with controls, and congregate abnormally near the lateral dermomyotome. In stripe assays, isolated muscle precursor cells avoid substrate-bound ephrin-A5 and this avoidance is abolished by addition of soluble ephrin-A5. These data suggest that ephrin-A5 normally restricts migrating, EphA4-positive muscle precursor cells to their appropriate territories in the forelimb, disallowing entry into abnormal embryonic regions.


2016 ◽  
Author(s):  
Jaeyoung Shin ◽  
Shuichi Watanabe ◽  
Soraya Hoelper ◽  
Marcus Krüger ◽  
Sawa Kostin ◽  
...  

2001 ◽  
Vol 281 (5) ◽  
pp. C1706-C1715 ◽  
Author(s):  
Patrick O. Mitchell ◽  
Grace K. Pavlath

Slow-twitch skeletal muscle atrophies greatly in response to unloading conditions. The cellular mechanisms that contribute to the restoration of muscle mass after atrophy are largely unknown. Here, we show that atrophy of the mouse soleus is associated with a 36% decrease in myonuclear number after 2 wk of hindlimb suspension. Myonuclear number is restored to control values during the 2-wk recovery period in which muscle mass returns to normal, suggesting that muscle precursor cells proliferate and fuse with myofibers. Inhibition of muscle precursor cell proliferation by local γ-irradiation of the hindlimb completely prevents this increase in myonuclear number. Muscle growth occurs normally during the first week in irradiated muscles, but growth during the second week is inhibited, leading to a 50% attenuation in the restoration of muscle mass. Thus early muscle growth occurs independently of an increase in myonuclear number, whereas later growth requires proliferating muscle precursor cells leading to myonuclear accretion. These results suggest that increasing the proliferative capacity of muscle precursor cells may enhance restoration of muscle mass after atrophy.


1996 ◽  
Vol 180 (2) ◽  
pp. 566-578 ◽  
Author(s):  
Silke Heymann ◽  
Maria Koudrova ◽  
H.-H. Arnold ◽  
Markus Köster ◽  
Thomas Braun

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 5061-5073 ◽  
Author(s):  
Annette Rau ◽  
Detlev Buttgereit ◽  
Anne Holz ◽  
Richard Fetter ◽  
Stephen K. Doberstein ◽  
...  

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.


2004 ◽  
Vol 298 (1) ◽  
pp. 48-57 ◽  
Author(s):  
F Raynaud ◽  
G Carnac ◽  
A Marcilhac ◽  
Y Benyamin

2004 ◽  
Vol 229 (3) ◽  
pp. 591-599 ◽  
Author(s):  
Sara J. Venters ◽  
Rebecca E. Argent ◽  
Fiona M. Deegan ◽  
Gina Perez-Baron ◽  
Ted S. Wong ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document