Lbx1 is required for muscle precursor migration along a lateral pathway into the limb

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 413-424 ◽  
Author(s):  
M.K. Gross ◽  
L. Moran-Rivard ◽  
T. Velasquez ◽  
M.N. Nakatsu ◽  
K. Jagla ◽  
...  
Keyword(s):  
Muscle Development ◽  
Muscle Loss ◽  
Limb Muscle ◽  
Lateral Migration ◽  
Muscle Precursor ◽  
Hindlimb Muscles ◽  
Limb Muscles ◽  
Mammalian Embryos ◽  
Myogenic Precursor ◽  
Hypaxial Muscle

In mammalian embryos, myogenic precursor cells emigrate from the ventral lip of the dermomyotome and colonize the limbs, tongue and diaphragm where they differentiate and form skeletal muscle. Previous studies have shown that Pax3, together with the c-Met receptor tyrosine kinase and its ligand Scatter Factor (SF) are necessary for the migration of hypaxial muscle precursors in mice. Lbx1 and Pax3 are co-expressed in all migrating hypaxial muscle precursors, raising the possibility that Lbx1 regulates their migration. To examine the function of Lbx1 in muscle development, we inactivated the Lbx1 gene by homologous recombination. Mice lacking Lbx1 exhibit an extensive loss of limb muscles, although some forelimb and hindlimb muscles are still present. The pattern of muscle loss suggests that Lbx1 is not required for the specification of particular limb muscles, and the muscle defects that occur in Lbx1(−/−) mice can be solely attributed to changes in muscle precursor migration. c-Met is expressed in Lbx1 mutant mice and limb muscle precursors delaminate from the ventral dermomyotome but fail to migrate laterally into the limb. Muscle precursors still migrate ventrally and give rise to tongue, diaphragm and some limb muscles, demonstrating Lbx1 is necessary for the lateral, but not ventral, migration of hypaxial muscle precursors. These results suggest that Lbx1 regulates responsiveness to a lateral migration signal which emanates from the developing limb.

Sonic hedgehog is a survival factor for hypaxial muscles during mouse development

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 743-752 ◽  
Author(s):  
M. Kruger ◽  
D. Mennerich ◽  
S. Fees ◽  
R. Schafer ◽  
S. Mundlos ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Muscle Development ◽  
Mouse Strains ◽  
Limb Muscle ◽  
Mouse Development ◽  
Vertebrate Embryos ◽  
Epaxial Muscles ◽  
Inactivating Mutations ◽  
Myogenic Precursor ◽  
Hypaxial Muscle

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.

No sexual dimorphism in limb muscles of a frog not engaging in amplexus

2013 ◽  
Vol 63 (4) ◽  
pp. 397-405
Author(s):  
Lixia Zhang ◽  
Yunyun Zhao ◽  
Jie Yang ◽  
Xin Lu ◽  
Xiaohong Chen
Keyword(s):  
Body Size ◽  
Sexual Dimorphism ◽  
Scramble Competition ◽  
Sexual Differences ◽  
Limb Muscle ◽  
Form And Function ◽  
Hindlimb Muscles ◽  
Limb Muscles ◽  
Forelimb Muscles ◽  
And Function

Sexual dimorphism in limb muscles is widespread among anurans, with males having stronger limbs than females. This phenomenon has been interpreted in the context of intrasexual selection: 1) the robust forelimb muscles in males are associated with amplexus, in which the male tries to grasp the female tightly, and also with rejection of rivals’ attempts at taking over, and 2) massive hindlimb muscles favor the ability to kick away rivals during scramble competition. However, in a few species, fertilization occurs without any form of amplexus and in these species the limb muscle dimorphism is expected to be absent. We tested this prediction inFeirana taihangnicus: a species without amplexus. As expected, we detected non-significant sexual differences in the mass of both forelimb and hindlimb muscles after accounting for body size and age. Our findings represent an interesting example of coevolution of form and function.

scholarly journals Pax-3 expression in segmental mesoderm marks early stages in myogenic cell specification

Development ◽  
1994 ◽  
Vol 120 (4) ◽  
pp. 785-796 ◽  
Author(s):  
B.A. Williams ◽  
C.P. Ordahl
Keyword(s):  
Muscle Development ◽  
Paraxial Mesoderm ◽  
Limb Muscle ◽  
Differential Modulation ◽  
Back Muscle ◽  
Cell Specification ◽  
Myogenic Lineage ◽  
Late Step ◽  
Myogenic Precursor ◽  
Migratory Cell

Specification of the myogenic lineage begins prior to gastrulation and culminates in the emergence of determined myogenic precursor cells from the somites. The myoD family (MDF) of transcriptional activators controls late step(s) in myogenic specification that are closely followed by terminal muscle differentiation. Genes expressed in myogenic specification at stages earlier than MDFs are unknown. The Pax-3 gene is expressed in all the cells of the caudal segmental plate, the early mesoderm compartment that contains the precursors of skeletal muscle. As somites form from the segmental plate and mature, Pax-3 expression is progressively modulated. Beginning at the time of segmentation, Pax-3 becomes repressed in the ventral half of the somite, leaving Pax-3 expression only in the dermomyotome. Subsequently, differential modulation of Pax-3 expression levels delineates the medial and lateral halves of the dermomyotome, which contain precursors of axial (back) muscle and limb muscle, respectively. Pax-3 expression is then repressed as dermomyotome-derived cells activate MDFs. Quail-chick chimera and ablation experiments confirmed that the migratory precursors of limb muscle continue to express Pax-3 during migration. Since limb muscle precursors do not activate MDFs until 2 days after they leave the somite, Pax-3 represents the first molecular marker for this migratory cell population. A null mutation of the mouse Pax-3 gene, Splotch, produces major disruptions in early limb muscle development (Franz, T., Kothary, R., Surani, M. A. H., Halata, Z. and Grim, M. (1993) Anat. Embryol. 187, 153–160; Goulding, M., Lumsden, A. and Paquette, A. (1994) Development 120, 957–971). We conclude, therefore, that Pax-3 gene expression in the paraxial mesoderm marks earlier stages in myogenic specification than MDFs and plays a crucial role in the specification and/or migration of limb myogenic precursors.

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.

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 ◽  
...  
Keyword(s):  
Cell Migration ◽  
Muscle Development ◽  
Potential Interaction ◽  
Precursor Cell ◽  
Limb Muscle ◽  
Potent Inducer ◽  
Muscle Precursor ◽  
Myoblast Cell ◽  
Muscle Precursor Cells ◽  
Muscle Precursor Cell

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.

scholarly journals Protein recycling and limb muscle recovery after critical illness in slow- and fast-twitch limb muscle

2019 ◽  
Vol 316 (5) ◽  
pp. R584-R593 ◽  
Author(s):  
Sebastien Preau ◽  
Michael Ambler ◽  
Anna Sigurta ◽  
Anna Kleyman ◽  
Alex Dyson ◽  
...  
Keyword(s):  
Critical Illness ◽  
Functional Disability ◽  
Ex Vivo ◽  
Therapeutic Option ◽  
Limb Muscle ◽  
Fungal Cell ◽  
Hindlimb Muscles ◽  
Initial Reduction ◽  
Male Wistar Rats

An impaired capacity of muscle to regenerate after critical illness results in long-term functional disability. We previously described in a long-term rat peritonitis model that gastrocnemius displays near-normal histology whereas soleus demonstrates a necrotizing phenotype. We thus investigated the link between the necrotizing phenotype of critical illness myopathy and proteasome activity in these two limb muscles. We studied male Wistar rats that underwent an intraperitoneal injection of the fungal cell wall constituent zymosan or n-saline as a sham-treated control. Rats ( n = 74) were killed at 2, 7, and 14 days postintervention with gastrocnemius and soleus muscle removed and studied ex vivo. Zymosan-treated animals displayed an initial reduction of body weight but a persistent decrease in mass of both lower hindlimb muscles. Zymosan increased chymotrypsin- and trypsin-like proteasome activities in gastrocnemius at days 2 and 7 but in soleus at day 2 only. Activated caspases-3 and -9, polyubiquitin proteins, and 14-kDa fragments of myofibrillar actin (proteasome substrates) remained persistently increased from day 2 to day 14 in soleus but not in gastrocnemius. These results suggest that a relative proteasome deficiency in soleus is associated with a necrotizing phenotype during long-term critical illness. Rescuing proteasome clearance may offer a potential therapeutic option to prevent long-term functional disability in critically ill patients.

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

1996 ◽  
Vol 180 (2) ◽  
pp. 566-578 ◽  
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

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.

EFFECTS OF SEX, GENOTYPE AND NUTRITION ON THE RELATIVE GROWTH OF MUSCLES IN THE PIG

1982 ◽  
Vol 62 (2) ◽  
pp. 587-596 ◽  
Author(s):  
R. J. RICHMOND ◽  
R. T. BERG
Keyword(s):  
Muscle Development ◽  
Muscle Growth ◽  
Abdominal Muscles ◽  
Relative Growth ◽  
Feeding Level ◽  
Thoracic Limb ◽  
Breed Differences ◽  
Limb Muscles ◽  
Pelvic Limb ◽  
Muscle Groups

The effects of liveweight, breed, sex, diet and feeding level on muscle distribution were studied by comparing nine anatomical muscle groups dissected from the half carcasses of pigs from two studies. The first study consisted of 109 pigs representing barrows and gilts of three breed groups, fed two diets differing in energy and protein. The second study consisted of 72 barrows and gilts from two breed groups fed a low-energy diet at one of three feed levels. Animals were slaughtered at 23, 68, 91 or 114 kg liveweight. The results were compared with data from one other study. In pigs, major differentiation in muscle development appears to take place prior to 23 kg liveweight. Muscle differentiation appeared to follow functional demands. Muscles associated with mobility immediately after birth such as the distal limb muscles, developed early while those associated with greater locomotion and propulsion, such as the proximal pelvic limb muscles, developed later in life. Sex had little influence on muscle distribution between 23 and 114 kg liveweight. Proportion of abdominal muscles had apparently increased markedly prior to 23 kg liveweight and continued to be influenced by the level of feeding throughout. Breed differences in muscle distribution were observed for spinal, abdominal and distal thoracic limb muscles. Key words: Swine, muscle growth, muscle distribution

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