Mox2 is a component of the genetic hierarchy controlling limb muscle development

Nature ◽  
10.1038/21892 ◽  
1999 ◽  
Vol 400 (6739) ◽  
pp. 69-73 ◽  
Author(s):  
Baljinder S. Mankoo ◽  
Nina S. Collins ◽  
Peter Ashby ◽  
Elena Grigorieva ◽  
Larysa H. Pevny ◽  
...  
Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 743-752 ◽  
Author(s):  
M. Kruger ◽  
D. Mennerich ◽  
S. Fees ◽  
R. Schafer ◽  
S. Mundlos ◽  
...  

Sonic hedgehog (Shh) has been proposed to function as an inductive and trophic signal that controls development of epaxial musculature in vertebrate embryos. In contrast, development of hypaxial muscles was assumed to occur independently of Shh. We here show that formation of limb muscles was severely affected in two different mouse strains with inactivating mutations of the Shh gene. The limb muscle defect became apparent relatively late and initial stages of hypaxial muscle development were unaffected or only slightly delayed. Micromass cultures and cultures of tissue fragments derived from limbs under different conditions with or without the overlaying ectoderm indicated that Shh is required for the maintenance of the expression of myogenic regulatory factors (MRFs) and, consecutively, for the formation of differentiated limb muscle myotubes. We propose that Shh acts as a survival and proliferation factor for myogenic precursor cells during hypaxial muscle development. Detection of a reduced but significant level of Myf5 expression in the epaxial compartment of somites of Shh homozygous mutant embryos at E9.5 indicated that Shh might be dispensable for the initiation of myogenesis both in hypaxial and epaxial muscles. Our data suggest that Shh acts similarly in both somitic compartments as a survival and proliferation factor and not as a primary inducer of myogenesis.


Apmis ◽  
2014 ◽  
Vol 122 (9) ◽  
pp. 766-771 ◽  
Author(s):  
Wang Li-Li ◽  
Peng Zhao-Hong ◽  
Fan Yang ◽  
Li Lian-Yong ◽  
Wu Di ◽  
...  

2016 ◽  
Vol 73 (23) ◽  
pp. 4415-4431 ◽  
Author(s):  
Marianne Deries ◽  
Sólveig Thorsteinsdóttir

1999 ◽  
Vol 10 (7) ◽  
pp. 2329-2342 ◽  
Author(s):  
Beth E. Stronach ◽  
Patricia J. Renfranz ◽  
Brenda Lilly ◽  
Mary C. Beckerle

A genetic hierarchy of interactions, involving myogenic regulatory factors of the MyoD and myocyte enhancer-binding 2 (MEF2) families, serves to elaborate and maintain the differentiated muscle phenotype through transcriptional regulation of muscle-specific target genes. Much work suggests that members of the cysteine-rich protein (CRP) family of LIM domain proteins also play a role in muscle differentiation; however, the specific functions of CRPs in this process remain undefined. Previously, we characterized two members of the Drosophila CRP family, the muscle LIM proteins Mlp60A and Mlp84B, which show restricted expression in differentiating muscle lineages. To extend our analysis ofDrosophila Mlps, we characterized the expression of Mlps in mutant backgrounds that disrupt specific aspects of muscle development. We show a genetic requirement for the transcription factor dMEF2 in regulating Mlp expression and an ability of dMEF2 to bind, in vitro, to consensus MEF2 sites derived from those present inMlp genomic sequences. These data suggest that theMlp genes may be direct targets of dMEF2 within the genetic hierarchy controlling muscle differentiation. Mutations that disrupt myoblast fusion fail to affect Mlp expression. In later stages of myogenic differentiation, which are dedicated primarily to assembly of the contractile apparatus, we analyzed the subcellular distribution of Mlp84B in detail. Immunofluorescent studies revealed the localization of Mlp84B to muscle attachment sites and the periphery of Z-bands of striated muscle. Analysis of mutations that affect expression of integrins and α-actinin, key components of these structures, also failed to perturb Mlp84B distribution. In conclusion, we have used molecular epistasis analysis to position Mlp function downstream of events involving mesoderm specification and patterning and concomitant with terminal muscle differentiation. Furthermore, our results are consistent with a structural role for Mlps as components of muscle cytoarchitecture.


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