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Biomedicine & Pharmacotherapy =... Feb 2023Targeted gene therapy has shown durable efficacy in non-neoplastic and neoplastic patients. Therefore, finding a suitable target has become a key area of research.... (Review)
Review
Targeted gene therapy has shown durable efficacy in non-neoplastic and neoplastic patients. Therefore, finding a suitable target has become a key area of research. Mesenchyme homeobox 1 (MEOX1) is a transcriptional factor that plays a significant role in regulation of somite development. Evidence indicates that abnormalities in MEOX1 expression and function are associated with a variety of pathologies, including non-neoplastic and neoplastic diseases. MEOX1 expression is upregulated during progression of most diseases and plays a critical role in maintenance of the cellular phenotypes such as cell differentiation, cell cycle arrest and senescence, migration, and proliferation. Therefore, MEOX1 may become an important molecular target and therapeutic target. This review will discuss the current state of knowledge on the role of MEOX1 in different diseases.
Topics: Humans; Homeodomain Proteins; Transcription Factors; Gene Expression Regulation; Cell Differentiation; Neoplasms; Cellular Senescence; Gene Expression Regulation, Neoplastic
PubMed: 36495659
DOI: 10.1016/j.biopha.2022.114068 -
International Journal of Molecular... Apr 2024During embryogenesis, basic fibroblast growth factor (bFGF) is released from neural tube and myotome to promote myogenic fate in the somite, and is routinely used for...
During embryogenesis, basic fibroblast growth factor (bFGF) is released from neural tube and myotome to promote myogenic fate in the somite, and is routinely used for the culture of adult skeletal muscle (SKM) stem cells (MuSC, called satellite cells). However, the mechanism employed by bFGF to promote SKM lineage and MuSC proliferation has not been analyzed in detail. Furthermore, the question of if the post-translational modification (PTM) of bFGF is important to its stemness-promoting effect has not been answered. In this study, GST-bFGF was expressed and purified from , which lacks the PTM system in eukaryotes. We found that both GST-bFGF and commercially available bFGF activated the Akt-Erk pathway and had strong cell proliferation effect on C2C12 myoblasts and MuSC. GST-bFGF reversibly compromised the myogenesis of C2C12 myoblasts and MuSC, and it increased the expression of , , and but strongly repressed that of , suggesting the maintenance of myogenic stemness amid repressed expression. The proliferation effect of GST-bFGF was conserved in C2C12 over-expressed with (C2C12-tTA-MyoD), implying its independence of the down-regulation of . In addition, the repressive effect of GST-bFGF on myogenic differentiation was almost totally rescued by the over-expression of . Together, these evidences suggest that (1) GST-bFGF and bFGF have similar effects on myogenic cell proliferation and differentiation, and (2) GST-bFGF can promote MuSC stemness and proliferation by differentially regulating and Pax3/7, (3) MyoD repression by GST-bFGF is reversible and independent of the proliferation effect, and (4) GST-bFGF can be a good substitute for bFGF in sustaining MuSC stemness and proliferation.
Topics: Muscle Development; Animals; Mice; MyoD Protein; Cell Proliferation; Fibroblast Growth Factor 2; Myoblasts; Cell Line; PAX7 Transcription Factor; PAX3 Transcription Factor; Myogenic Regulatory Factor 5; Cyclin D1; Satellite Cells, Skeletal Muscle; Cell Differentiation; Proto-Oncogene Proteins c-akt; Muscle, Skeletal
PubMed: 38673893
DOI: 10.3390/ijms25084308 -
ELife Jan 2022During the development of the vertebrate embryo, segmented structures called somites are periodically formed from the presomitic mesoderm (PSM) and give rise to the...
During the development of the vertebrate embryo, segmented structures called somites are periodically formed from the presomitic mesoderm (PSM) and give rise to the vertebral column. While somite formation has been studied in several animal models, it is less clear how well this process is conserved in humans. Recent progress has made it possible to study aspects of human paraxial mesoderm (PM) development such as the human segmentation clock using human pluripotent stem cells (hPSCs); however, somite formation has not been observed in these monolayer cultures. Here, we describe the generation of human PM organoids from hPSCs (termed Somitoids), which recapitulate the molecular, morphological, and functional features of PM development, including formation of somite-like structures . Using a quantitative image-based screen, we identify critical parameters such as initial cell number and signaling modulations that reproducibly yielded formation of somite-like structures in our organoid system. In addition, using single-cell RNA-sequencing and 3D imaging, we show that PM organoids both transcriptionally and morphologically resemble their counterparts and can be differentiated into somite derivatives. Our organoid system is reproducible and scalable, allowing for the systematic and quantitative analysis of human spine development and disease .
Topics: Animals; Cell Differentiation; Humans; Mesoderm; Organoids; Pluripotent Stem Cells; Somites
PubMed: 35088712
DOI: 10.7554/eLife.68925 -
Physiology (Bethesda, Md.) Mar 2023The significance of the coupling delay, which is the time required for interactions between coupled oscillators, in various oscillatory dynamics has been investigated... (Review)
Review
The significance of the coupling delay, which is the time required for interactions between coupled oscillators, in various oscillatory dynamics has been investigated mathematically for more than three decades, but its biological significance has been revealed only recently. In the segmentation clock, which regulates the periodic formation of somites in embryos, Hes7 expression oscillates synchronously between neighboring presomitic mesoderm (PSM) cells, and this synchronized oscillation is controlled by Notch signaling-mediated coupling between PSM cells. Recent studies have shown that inappropriate coupling delays dampen and desynchronize Hes7 oscillations, as simulated mathematically, leading to the severe fusion of somites and somite-derived tissues such as the vertebrae and ribs. These results indicate the biological significance of the coupling delay in synchronized Hes7 oscillations in the segmentation clock. The recent development of an in vitro PSM-like system will facilitate the detailed analysis of the coupling delay in synchronized oscillations.
Topics: Humans; Basic Helix-Loop-Helix Transcription Factors; Somites; Signal Transduction
PubMed: 36256636
DOI: 10.1152/physiol.00023.2022 -
Journal of Molecular Endocrinology Nov 2022Vitamin A (retinol) is an important nutrient for embryonic development and adult health. Early studies identified retinoic acid (RA) as a metabolite of retinol, however,...
Vitamin A (retinol) is an important nutrient for embryonic development and adult health. Early studies identified retinoic acid (RA) as a metabolite of retinol, however, its importance was not apparent. Later, it was observed that RA treatment of vertebrate embryos had teratogenic effects on limb development. Subsequently, the discovery of nuclear RA receptors (RARs) revealed that RA controls gene expression directly at the transcriptional level through a process referred to as RA signaling. This important discovery led to further studies demonstrating that RA and RARs are required for normal embryonic development. The determination of RA function during normal development has been challenging as RA gain-of-function studies often lead to conclusions about normal development that conflict with RAR or RA loss-of-function studies. However, genetic loss-of-function studies have identified direct target genes of endogenous RA/RAR that are required for normal development of specific tissues. Thus, genetic loss-of-function studies that eliminate RARs or RA-generating enzymes have been instrumental in revealing that RA signaling is required for normal early development of many organs and tissues, including the hindbrain, posterior body axis, somites, spinal cord, forelimbs, heart, and eye.
Topics: Animals; Carrier Proteins; Female; Pregnancy; Receptors, Retinoic Acid; Signal Transduction; Tretinoin; Vitamin A
PubMed: 35593389
DOI: 10.1530/JME-22-0041 -
Frontiers in Oncology 2023MAP4K4 is a serine/threonine kinase that belongs to the MAP kinase family and plays a critical role in embryogenesis and cellular migration. It contains approximately... (Review)
Review
MAP4K4 is a serine/threonine kinase that belongs to the MAP kinase family and plays a critical role in embryogenesis and cellular migration. It contains approximately 1,200 amino acids and has a molecular mass of 140 kDa. MAP4K4 is expressed in most tissues where it has been examined and its knockout is embryonic lethal due to impaired somite development. Alterations in MAP4K4 function have a central role in the development of many metabolic diseases such as atherosclerosis and type 2 diabetes, but have recently been implicated in the initiation and progression of cancer. For example, it has been shown that MAP4K4 can stimulate the proliferation and invasion of tumor cells by activating pro-proliferative pathways (such as the c-Jun N-terminal kinase [JNK] and mixed-lineage protein kinase 3 [MLK3] pathways), attenuate anti-tumor cytotoxic immune responses, and stimulate cell invasion and migration by altering cytoskeleton and actin function. Recent experiments using RNA interference-based knockdown (miR) techniques have shown that inhibition of MAP4K4 function reduces tumor proliferation, migration, and invasion, and may represent a promising therapeutic approach in many types of cancer such as pancreatic cancer, glioblastoma, and medulloblastoma, among others. Over the last few years, specific MAP4K4 inhibitors such as GNE-495 have been developed but have not yet been tested in cancer patients. However, these novel agents may be useful for cancer treatment in the future.
PubMed: 37223681
DOI: 10.3389/fonc.2023.1162835 -
Zoological Research May 2023The biological function of the novel zinc-finger SWIM domain-containing protein family (ZSWIM) during embryonic development remains elusive. Here, we conducted a...
The biological function of the novel zinc-finger SWIM domain-containing protein family (ZSWIM) during embryonic development remains elusive. Here, we conducted a genome-wide analysis to explore the evolutionary processes of the gene family members in mice, , zebrafish, and humans. We identified nine putative genes in the human and mouse genome, eight in the genome, and five in the zebrafish genome. Based on multiple sequence alignment, three members, ZSWIM5, ZSWIM6, and ZSWIM8, demonstrated the highest homology across all four species. Using available RNA sequencing (RNA-seq) data, genes were found to be widely expressed across different tissues, with distinct tissue-specific properties. To identify the functions of the ZSWIM protein family during embryogenesis, we examined temporal and spatial expression patterns of family genes in embryos Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that each member had a distinct expression profile. Whole-mount hybridization showed that both and were maternally expressed genes; and were expressed throughout embryogenesis and displayed dynamic expression in the brain, eyes, somite, and bronchial arch at the late tailbud stages; was detected in the eye area; showed a dynamic expression pattern during the tailbud stages, with expression detected in the brain, eyes, and somite; was faintly expressed throughout embryonic development. This study provides a foundation for future research to delineate the functions of gene members.
Topics: Female; Pregnancy; Humans; Animals; Mice; Zebrafish; Xenopus; Biological Evolution; Brain; Zinc Fingers; DNA-Binding Proteins
PubMed: 37161653
DOI: 10.24272/j.issn.2095-8137.2022.418 -
Frontiers in Cell and Developmental... 2021Somites are transitory metameric structures at the basis of the axial organization of vertebrate musculoskeletal system. During evolution, somites appear in the chordate...
Somites are transitory metameric structures at the basis of the axial organization of vertebrate musculoskeletal system. During evolution, somites appear in the chordate phylum and compartmentalize mainly into the dermomyotome, the myotome, and the sclerotome in vertebrates. In this review, we summarized the existing literature about somite compartmentalization in and compared it with other anamniote and amniote vertebrates. We also present and discuss a model that describes the evolutionary history of somite compartmentalization from ancestral chordates to amniote vertebrates. We propose that the ancestral organization of chordate somite, subdivided into a lateral compartment of multipotent somitic cells (MSCs) and a medial primitive myotome, evolves through two major transitions. From ancestral chordates to vertebrates, the cell potency of MSCs may have evolved and gave rise to all new vertebrate compartments, i.e., the dermomyome, its hypaxial region, and the sclerotome. From anamniote to amniote vertebrates, the lateral MSC territory may expand to the whole somite at the expense of primitive myotome and may probably facilitate sclerotome formation. We propose that successive modifications of the cell potency of some type of embryonic progenitors could be one of major processes of the vertebrate evolution.
PubMed: 35111756
DOI: 10.3389/fcell.2021.790847 -
Frontiers in Neuroanatomy 2023The larynx is an organ of the upper airway that participates in breathing, glutition, voice production, and airway protection. These complex functions depend on vocal... (Review)
Review
The larynx is an organ of the upper airway that participates in breathing, glutition, voice production, and airway protection. These complex functions depend on vocal fold (VF) movement, facilitated in turn by the action of the intrinsic laryngeal muscles (ILM). The necessary precise and near-instantaneous modulation of each ILM contraction relies on proprioceptive innervation of the larynx. Dysfunctional laryngeal proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia, vocal fold paresis, and paralysis. While the proprioceptive system in skeletal muscle derived from somites is well described, the proprioceptive circuitry that governs head and neck structures such as VF has not been so well characterized. For over two centuries, researchers have investigated the question of whether canonical proprioceptive organs, muscle spindles, and Golgi tendon organs, exist in the ILM, with variable findings. The present work is a state-of-the-art review of the peripheral component of laryngeal proprioception, including current knowledge of canonical and possible alternative proprioceptive circuitry elements in the larynx.
PubMed: 36910514
DOI: 10.3389/fnana.2023.1114817