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 The Role of Purinergic Receptors in Cancer-Induced Bone Pain

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sarah Falk ◽  
Maria Uldall ◽  
Anne-Marie Heegaard
Keyword(s):  
Inflammatory Pain ◽  
Bone Pain ◽  
Purinergic Receptors ◽  
Sensory Information ◽  
Cellular Mechanisms ◽  
Pain State ◽  
Current Therapies ◽  
Peripheral Site

Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular mechanisms underlying cancer-induced bone pain including the involvement of ATP and the purinergic receptors in the progression of the pain state. In nociception, ATP acts as an extracellular messenger to transmit sensory information both at the peripheral site of tissue damage and in the spinal cord. Several of the purinergic receptors have been shown to be important for the development and maintenance of neuropathic and inflammatory pain, and studies have demonstrated the importance of both peripheral and central mechanisms. We here provide an overview of the current literature on the role of purinergic receptors in cancer-induced bone pain with emphasis on some of the difficulties related to studying this complex pain state.

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.

Antagonistic role of vitamin D3 and retinoic acid on the differentiation of chicken hematopoietic macrophages into osteoclast precursor cells.

Endocrinology ◽  
1995 ◽  
Vol 136 (1) ◽  
pp. 85-95 ◽  
Author(s):  
C Woods ◽  
C Domenget ◽  
F Solari ◽  
O Gandrillon ◽  
E Lazarides ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin D3 ◽  
Precursor Cells ◽  
Osteoclast Precursor

The Role of Transcriptional Coactivator TRAP220/MED1 in Nuclear Receptor-Mediated Myelomonocytic Differentiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2727-2727
Author(s):  
Mitsuhiro Ito ◽  
Norinaga Urahama ◽  
Akiko Sada ◽  
Kimikazu Yakushijin ◽  
Katsuya Yamamoto ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Precursor Cells ◽  
Mediator Complex ◽  
Dihydroxyvitamin D3 ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Hematopoietic Precursor

Abstract The TRAP/Mediator complex, the metazoan counterpart of the yeast Mediator complex, is master transcriptional regulatory complex composed of approximately 30 subunits. It was originally isolated as a thyroid hormone receptor (TR)-associated protein (TRAP) complex that mediates TR-activated transcription from DNA templates in vitro and probably acts in vivo after the action of other receptor-interacting coactivators involved in chromatin remodeling. The TRAP220/MED1 subunit of the TRAP/Mediator complex is proposed to act on a variety of major and specific biological events, including growth, differentiation and homeostasis, through physical interaction with nuclear receptors. The vitamin D receptor (VDR) and retinoic acid receptor (RAR), coupled with retinoid X receptor (RXR), are nuclear receptors which have important roles for monopoiesis and granulopoiesis, respectively. In this study, we present the functional role of TRAP220/MED1 in nuclear receptor-mediated monopoiesis and granulopoiesis. Since TRAP220 knockout (Trap220-/-) mice were mortalities during the early embryonic period before definitive hematopoiesis within the hepatic primordia becomes dominant, the function of TRAP220/MED1 in adult hematopoiesis was mostly unknown. However, these embryos appeared to have normal composition of nucleated erythroid cells. Therefore, the E9.0 yolk sac-derived hematopoietic precursor cells were used to differentiate into definitive hematopoietic colony forming units within the methylcellulose blood cell culture. The number of monocytic colonies (CFU-M) was significantly lower in knockouts than in wild type controls, while the numbers of other types of colonies (CFU-GEMM, CFU-GM, CFU-G and CFU-E) were comparable. Hence, TRAP220/MED1 appeared to be indispensable for optimal monocytic differentiation. Next, the HL-60 acute promyelocytic leukemia cells were used to elucidate directly and mechanistically the roles of TRAP220/MED1 in RAR- and VDR-dependent differentiation of the hematopoietic precursor cells into granulocytic and monocytic lineage cells. The expression of the TRAP220/MED1 subunit as well as other TRAP/Mediator subunits was induced when the cells were treated with their ligands, all-trans retinoic acid and 1,25-dihydroxyvitamin D3. Flow cytometric analyses showed that HL-60 cells, wherein TRAP220/MED1 was down-regulated, did not differentiate efficiently into monocytes and granulocytes by stimulation with 1,25-dihydroxyvitamin D3 and all-trans retinoic acid, correspondingly. The expression of direct target genes of VDR or RAR, as well as the differentiation marker genes, was low in the knockdown cells by stimulation with these ligands. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA)- and dimethylsulphoxide (DMSO)-mediated monocytic and myeloid differentiation, which bypasses nuclear receptor-mediated signaling pathways, was not affected in knockdown cells. Collectively, these results indicated an indispensable role of TRAP220/MED1 in the optimal VDR- and RAR-mediated myelomonocytic differentiation processes in mammalian hematopoiesis.

scholarly journals Regeneration of hemopoietic precursor cells in spleen organ cultures from irradiated mice: influence of genotype of cells injected and of the spleen microenvironment

Blood ◽  
1981 ◽  
Vol 57 (5) ◽  
pp. 906-912
Author(s):  
H von Melchner ◽  
GJ Lieschke
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Precursor Cells ◽  
Recipient Strain ◽  
Allogeneic Bone ◽  
Donor Strain ◽  
Organ Cultures ◽  
Hemopoietic Precursor Cells

The regeneration of hemopoietic precursor cells (colony-forming cells, CFC) was monitored in spleen organ cultures from lethally irradiated mice injected with 10(7) normal syngeneic or allogeneic bone marrow cells. The important role of the microenvironment in supporting hemopoiesis was confirmed by the failure of mutant S1/S1d spleens to support CFC regeneration in organ cultures. However, the extent and quality of the CFC regeneration was clearly dependent on the genetic properties of the injected cells. Evidence for this was obtained from the regeneration patterns of various CFC types in organ cultured spleens derived from different mouse donor-recipient strain combinations (CBA/CBA, CBA/C57BL, CBA/BALB/c, C57BL/C57BL, C57BL/CBA, C57BL/BALB/c) that maintained the differences in the bone marrow frequency of various CFC types characteristic of the donor strain.

scholarly journals Convergence of Synapses, Endosomes, and Prions in the Biology of Neurodegenerative Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Gunnar K. Gouras
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Brain Regions ◽  
Neural Function ◽  
Cellular Mechanisms ◽  
Normal Functions ◽  
Age Related ◽  
Cell Propagation

Age-related misfolding and aggregation of disease-linked proteins in selective brain regions is a characteristic of neurodegenerative diseases. Although neuropathological aggregates that characterize these various diseases are found at sites other than synapses, increasing evidence supports the idea that synapses are where the pathogenesis begins. Understanding these diseases is hampered by our lack of knowledge of what the normal functions of these proteins are and how they are affected by aging. Evidence has supported the idea that neurodegenerative disease-linked proteins have a common propensity for prion protein-like cell-to-cell propagation. However, it is not thought that the prion-like quality of these proteins/peptides that allows their cell-to-cell transmission implies a role for human-to-human spread in common age-related neurodegenerative diseases. It will be important to better understand the molecular and cellular mechanisms governing the role of these aggregating proteins in neural function, especially at synapses, how their propagation occurs and how pathogenesis is promoted by aging.

scholarly journals Regeneration of hemopoietic precursor cells in spleen organ cultures from irradiated mice: influence of genotype of cells injected and of the spleen microenvironment

Blood ◽  
1981 ◽  
Vol 57 (5) ◽  
pp. 906-912 ◽  
Author(s):  
H von Melchner ◽  
GJ Lieschke
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Precursor Cells ◽  
Recipient Strain ◽  
Allogeneic Bone ◽  
Donor Strain ◽  
Organ Cultures ◽  
Hemopoietic Precursor Cells

Abstract The regeneration of hemopoietic precursor cells (colony-forming cells, CFC) was monitored in spleen organ cultures from lethally irradiated mice injected with 10(7) normal syngeneic or allogeneic bone marrow cells. The important role of the microenvironment in supporting hemopoiesis was confirmed by the failure of mutant S1/S1d spleens to support CFC regeneration in organ cultures. However, the extent and quality of the CFC regeneration was clearly dependent on the genetic properties of the injected cells. Evidence for this was obtained from the regeneration patterns of various CFC types in organ cultured spleens derived from different mouse donor-recipient strain combinations (CBA/CBA, CBA/C57BL, CBA/BALB/c, C57BL/C57BL, C57BL/CBA, C57BL/BALB/c) that maintained the differences in the bone marrow frequency of various CFC types characteristic of the donor strain.

scholarly journals Circular RNA screening identifies circMYLK4 as a regulator of fast/slow myofibers in porcine skeletal muscles

2021 ◽  
Author(s):  
Haigang Cao ◽  
Jieming Liu ◽  
Tianning Du ◽  
Yihao Liu ◽  
Xiaoyu Zhang ◽  
...  
Keyword(s):  
Muscle Development ◽  
Circular Rna ◽  
Marker Genes ◽  
Skeletal Muscle Development ◽  
Type Conversion ◽  
Protein Levels ◽  
Skeletal Myofiber ◽  
Myofiber Type

AbstractThe type of myofiber is related to the quality of meat. The slow oxidized myofiber helps to increase the tenderness and juiciness of muscle. Numerous studies have shown that circRNA plays a key role in skeletal muscle development. However, the role of circRNA in porcine skeletal myofiber types is unclear. In this study, we performed high-throughput RNA sequencing to study the differential expression of circRNA in the longissimus dorsi and the soleus muscle. A total of 40,757 circRNAs were identified, of which 181 were significantly different. Interestingly, some circRNAs were involved in metabolism pathways, AMPK, FoxO, and PI3K-Akt signaling pathways. Besides, we focused on a novel circRNA-circMYLK4. By injecting circMYLK4-AAV into piglets, we found that circMYLK4 significantly increased the mRNA and protein levels of the slow muscle marker genes. In summary, our study laid an essential foundation for further research of circRNA in myofiber type conversion and higher meat quality.

Non-overlapping expression of CRBP I and CRABP I during pattern formation of limbs and craniofacial structures in the early mouse embryo

Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 451-460 ◽  
Author(s):  
A.L. Gustafson ◽  
L. Dencker ◽  
U. Eriksson
Keyword(s):  
Retinoic Acid ◽  
Pattern Formation ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Surface Ectoderm ◽  
Early Mouse Embryo ◽  
Crabp I ◽  
Pregnant Mice ◽  
Early Mouse

Retinoic acid (RA), a physiological metabolite of retinol (vitamin A), is thought to be of importance for pattern formation in the developing embryo. However, the mechanism by which RA is generated, as well as the site of its formation in the developing embryo, is still unknown. In this paper, we show that radiolabelled retinol, administered to pregnant mice, is accumulated in specific locations in the embryos. As revealed by immunohistochemistry using antibodies to cellular retinol-binding protein I (CRBP I), retinol accumulates in regions of the embryo expressing CRBP I. In limbs and craniofacial structures, CRBP I expression and retinol accumulation was seen in endoderm and surface ectoderm. Most mesenchymal cells of the limbs and craniofacial structures did not express detectable levels of CRBP I but instead expressed cellular retinoic acid-binding protein I (CRABP I). Previous results have demonstrated that CRABP I is involved in accumulation of RA in the embryo. Thus, the spatially closely related but non-overlapping domains of expression of CRBP I and CRABP I suggests a role of a retinol/RA pathway in epithelial-mesenchymal interactions during pattern formation of limbs and of craniofacial structures.

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.

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