Hedgehog signaling regulates the amount of hypaxial muscle development during Xenopus myogenesis

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.

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Hedgehog signaling and laminin play unique and synergistic roles in muscle development

Developmental Dynamics ◽

10.1002/dvdy.22204 ◽

2010 ◽

Vol 239 (3) ◽

pp. 905-913 ◽

Cited By ~ 11

Author(s):

Matthew T. Peterson ◽

Clarissa A. Henry

Keyword(s):

Hedgehog Signaling ◽

Muscle Development

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Regulation of hypaxial muscle development

Cell and Tissue Research ◽

10.1007/s004410051278 ◽

1999 ◽

Vol 296 (1) ◽

pp. 175-182 ◽

Cited By ~ 57

Author(s):

Susanne Dietrich

Keyword(s):

Muscle Development ◽

Hypaxial Muscle

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Time Course Transcriptome Analysis of Spina Bifida Progression in Fetal Rats

Brain Sciences ◽

10.3390/brainsci11121593 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1593

Author(s):

Kendall P. Murphy ◽

Bedika Pathak ◽

Jose L. Peiro ◽

Marc Oria

Keyword(s):

Spina Bifida ◽

Hedgehog Signaling ◽

Time Course ◽

Muscle Development ◽

Interaction Analysis ◽

Differentially Expressed ◽

Significant Variable ◽

Spinal Cord Regeneration ◽

Surgical Interventions ◽

Time Points

A better understanding of the transcriptomic modifications that occur in spina bifida may lead to identify mechanisms involved in the progression of spina bifida in utero and the development of new therapeutic strategies that aid in spinal cord regeneration after surgical interventions. In this study, RNA-sequencing was used to identify differentially expressed genes in fetal spinal cords from rats with retinoic acid-induced spina bifida at E15, E17, and E20. Gene ontology, KEGG, and protein–protein interaction analysis were conducted to predict pathways involved in the evolution of the disease. Approximately 3000, 1000 and 300 genes were differentially expressed compared to the control groups at E15, E17 and E20, respectively. Overall, the results suggest common alterations in certain pathways between gestational time points, such as upregulation in p53 and sonic hedgehog signaling at E15 and E17 and downregulation in the myelin sheath at E17 and E20. However, there were other modifications specific to gestational time points, including skeletal muscle development at E15, downregulated glucose metabolism at E17, and upregulated inflammation at E20. In conclusion, this work provides evidence that gestational age during spina bifida repair may be a significant variable to consider during the development of new regenerative therapeutics approaches.

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

Development ◽

10.1242/dev.127.2.413 ◽

2000 ◽

Vol 127 (2) ◽

pp. 413-424 ◽

Cited By ~ 5

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.

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Hypaxial Muscle Development

Results and Problems in Cell Differentiation - Vertebrate Myogenesis ◽

10.1007/978-3-540-45686-5_6 ◽

2002 ◽

pp. 127-141 ◽

Cited By ~ 5

Author(s):

Gary Parkyn ◽

Roy C. Mootoosamy ◽

Louise Cheng ◽

Colin Thorpe ◽

Susanne Dietrich

Keyword(s):

Muscle Development ◽

Hypaxial Muscle

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Human engineered skeletal muscle of hypaxial origin from pluripotent stem cells with advanced function and regenerative capacity

10.1101/2021.07.12.452030 ◽

2021 ◽

Author(s):

Mina Shahriyari ◽

Md Islam ◽

M Sakib ◽

Anastasia Rika ◽

Dennis Krueger ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Satellite Cell ◽

Pluripotent Stem Cells ◽

Cell Activation ◽

Muscle Development ◽

Underlying Mechanism ◽

Hypaxial Muscle

Human pluripotent stem cell derived muscle models show great potential for translational research. Here, we describe developmentally inspired methods for derivation of skeletal muscle cells and their utility in three-dimensional skeletal muscle organoid formation as well as skeletal muscle tissue engineering. Key steps include the directed differentiation of human pluripotent stem cells to embryonic muscle progenitors of hypaxial origin followed by primary and secondary fetal myogenesis into hypaxial muscle with development of a satellite cell pool and evidence for innervation in vitro. Skeletal muscle organoids faithfully recapitulate all steps of embryonic myogenesis in 3D. Tissue engineered muscle exhibits organotypic maturation and function, advanced by thyroid hormone. Regenerative competence was demonstrated in a cardiotoxin injury model with evidence of satellite cell activation as underlying mechanism. Collectively, we introduce a hypaxial muscle model with canonical properties of bona fide skeletal muscle in vivo to study muscle development, maturation, disease, and repair.

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Smoothened Signaling in Vertebrates Is Facilitated by a G Protein-coupled Receptor Kinase

Molecular Biology of the Cell ◽

10.1091/mbc.e08-05-0448 ◽

2008 ◽

Vol 19 (12) ◽

pp. 5478-5489 ◽

Cited By ~ 45

Author(s):

Melanie Philipp ◽

Gregory B. Fralish ◽

Alison R. Meloni ◽

Wei Chen ◽

Alyson W. MacInnes ◽

...

Keyword(s):

Signal Transduction ◽

G Protein ◽

Hedgehog Signaling ◽

Muscle Development ◽

Molecular Architecture ◽

Neural Patterning ◽

Transcriptional Responses ◽

Protein Functions ◽

G Protein Coupled ◽

Hedgehog Signal

Smoothened, a heptahelical membrane protein, functions as the transducer of Hedgehog signaling. The kinases that modulate Smoothened have been thoroughly analyzed in flies. However, little is known about how phosphorylation affects Smoothened in vertebrates, mainly, because the residues, where Smoothened is phosphorylated are not conserved from Drosophila to vertebrates. Given its molecular architecture, Smoothened signaling is likely to be regulated in a manner analogous to G protein–coupled receptors (GPCRs). Previously, it has been shown, that arrestins and GPCR kinases, (GRKs) not only desensitize G protein–dependent receptor signaling but also function as triggers for GPCR trafficking and formation of signaling complexes. Here we describe that a GRK contributes to Smoothened-mediated signaling in vertebrates. Knockdown of the zebrafish homolog of mammalian GRK2/3 results in lowered Hedgehog transcriptional responses, impaired muscle development, and neural patterning. Results obtained in zebrafish are corroborated both in cell culture, where zGRK2/3 phosphorylates Smoothened and promotes Smoothened signal transduction and in mice where deletion of GRK2 interferes with neural tube patterning. Together, these data suggest that a GRK functions as a vertebrate kinase for Smoothened, promoting Hedgehog signal transduction during early development.

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Alterations in Ultrastructure of Skeletal Muscle From Newborn Guinea Pigs Following in Utero Exposure to Ethanol

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120126 ◽

1985 ◽

Vol 43 ◽

pp. 686-687

Author(s):

C. Uphoff ◽

C. Nyquist-Battie ◽

T.B. Cole

Keyword(s):

Skeletal Muscle ◽

Guinea Pigs ◽

Muscle Development ◽

In Utero ◽

Ethanol Exposure ◽

Prenatally Exposed ◽

Chronic Alcoholic ◽

Test Kit ◽

Food And Water Intake ◽

Post Intubation

Ultrastructural alterations of skeletal muscle have been observed in adult chronic alcoholic patients. However, no such study has been performed on individuals prenatally exposed to ethanol. In order to determine if ethanol exposure in utero in the latter stages of muscle development was deleterious, skeletal muscle was obtained from newborn guinea pigs treated in the following manner. Six Hartly strain pregnant guinea pigs were randomly assigned to either the ethanol or the pair-intubated groups. Twice daily the 3 ethanol-treated animals were intubated with Ensure (Ross Laboratories) liquid diet containing 30% ethanol (6g/Kg pre-pregnant body weight per day) from day 35 of gestation until parturition at day 70±1 day. Serum ethanol levels were determined at 1 hour post-intubation by the Sigma alcohol test kit. For pair-intubation the Ensure diet contained sucrose substituted isocalorically for ethanol. Both food and water intake were monitored.

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