Research Area

Muscular System Development


Muscular system overview

According to the shape and distribution of muscle tissue, it can be divided into three types: striated muscle tissue, smooth muscle tissue, and myocardial tissue. smooth muscle cannot be controlled by the will, so it is also called involuntary muscle. It is composed of slender cells or muscle fibers, without horizontal stripes, and is mainly distributed on the peripheral wall of hollow organs in the body. Smooth muscles of the internal organs, respiratory tract and urethra account for 5%-10% of the body's body weight. The myocardium is the most important muscle in the human body. It is made up of muscle fibers interwoven in an extremely complicated way to form the heart wall.

Muscular system development regulation

The meat production of animals is closely related to the number and growth of muscle fiber cells. Myofibroblasts are formed by myeloblasts in the early stages of embryonic development through hyperplasia and hypertrophy. In recent years, due to the development of molecular genetics, the innovation of molecular biology techniques, the culture technology of in vitro cell lines, and the maturation of gene targeting technology, the regulation of the differentiation, growth and development of muscle cells has been made in the molecule. There is a deeper understanding of the level. Functional genes and their regulatory mechanisms of muscle cell differentiation and growth are regulated bidirectionally by some positive regulatory factors and negative regulatory factors. The insulin-like growth factor (IGF) axis is thought to have an important positive regulatory role in the differentiation and growth of muscle cells. IGFs increase the molecular expression during the formation of secondary fibers, and its role is to stimulate myoblast proliferation. Maintain the differentiation of muscle fibers. Muscle growth requires myoblast proliferation and differentiation of MyoD (myogenic determination gene, or myogenic factor or myogenic regulatory factor, MRF) family genes. The myogenic factor (MyoD) includes four genes,myod1 (myf3), myogenin (myoG), myf5, myf-6 (herculin or mrf4). The myod family of genes belongs to the myogenic alkaline helix-loop-helix (bHLH) transcription factor, which activates muscle-specific genes. MyoD works by regulating the actin gene. The mammalian striated muscle actin gene promoter contains several transcription factors binding sites, of which E-box is the myogenic factor myoD and Myogenin binding site. MyoD1 and Myogenin have a Myc homology region, a member of the gene family that regulates myogenesis, and is used together for the differentiation and growth of myocytes. The expression of myogenin has the effect of controlling the initiation of myoblast fusion, promoting the proliferation of myoblasts, and transforming mononuclear myoblasts into multinucleated myofibers. Therefore, Myogenin is central to the MyoD family. MyoD is regulated by protein kinase (PKC) and calmodulin. The differentiation and growth of myocytes are affected by negative regulatory factors. MyoD inhibintor (I-MFA, an inhibitor of the MyoD family) is a transcriptional regulator that negatively controls muscle cell growth and development by inhibiting the transcriptional activity of MyoD family members. I-MFA is expressed in the osteoblast cell line (MC3T3E1), VD3 promotes I-MFA mRNA expression, and I-MFA is inhibited by RNA polymerase inhibitor, but not by protein synthesis inhibitor. Myostatin (MSTN, also known as GDF-8, growth differentiation factor 8) belongs to the transforming growth factor bata and is an important regulator of myocyte growth in recent years. By inhibiting the transcriptional activity of MyoD family members negatively controlling the growth and development of muscle cells, its expression was negatively correlated with changes in muscle mass. It is expressed in the fetal muscles of mice and is detectable in almost all skeletal muscles in adulthood. Studies have shown that muscle atrophy in rats after spaceflight is due to an increase in the mRNA and protein levels of myostatin and a decrease in IGF-II mRNA in skeletal muscle. Myostatin inhibits the differentiation of pre-adipocytes of 3T3-L1 and reduces the activity of glycerol-3-phosphate dehydrogenase. 01dham (2001) demonstrated that the IGF axis is not different between the double muscle cattle and the normal cattle. IGF-II mRNA increases in the secondary fiber formation of both varieties. However, both MyoD and Myostatin are significantly different. The loss of Myostatin is related to the number of muscle fibers, which can significantly increase muscle production in double-muscled cattle, and MyoD is also very important.

Muscular system development research status

Recent studies have found that LncRNAs can competitively bind to other non-coding RNAs (including microRNAs) and jointly regulate gene expression. There is a class of competitive endogenous RNA (ceRNA)-lncRNA that binds to miRNAs and blocks the action of miRNAs on target genes, ensuring the post-transcriptional expression of the corresponding target genes. Cesana et al found that the cytoplasmic long-chain non-coding RNAlinc-MD1 can specifically exert ceRNA activity in the study of human and mouse skeletal muscle growth and is specific to muscle by binding to miR-133 and miR-135. Regulation of the expression of sex genes, the transcriptional regulators MAML1 and MEF2C. lncRNA can be used as a decoy molecule to affect skeletal muscle growth and apoptosis. Growth arrest-specific transcript 5 (Gas5) is a mammalian muscle growth and apoptosis. Key regulator Gas5 binds to the glucocorticoid receptor's DNA domain by mimicking the glucocorticoid response element, preventing the interaction of the glucocorticoid receptor with the glucocorticoid response element, thereby inhibiting downstream gene expression and promoting cell wilting. P53 directly induced the expression of long intergenic ncRNA p21 (lincRNA-p21), and LincRNA-p21 was able to interact with nuclear heterogeneous ribonucleoprotein-K (hnRNP-K). Interactions inhibit the expression of genes downstream of the p53 signaling pathway, thereby modulating p53-mediated apoptosis. LncRNA may have a remote regulation of growth and development mechanism LncRNA IGF2R antisense RNA (antisense of IGF2R RNA, AIR), XIST, etc., by the formation of chromatin-modifying complexes to silence neighboring gene transcription, homeobox gene (HOX) plays a key role in cell proliferation and directional differentiation. The discovery of Hox antisense intergenic RNA (HOTAIR) suggests that lncRNA may have a role in the remote regulation of muscle growth and development, in which HOTAIR is located at HOXC locus 12q13.13, and the 5' end of HOTAIR can be recruited for binding. Multi-comb Protein inhibition complex 2 (PRC2), with the help of three H3K27 methylases SUZ12, EED and EZH2 on PRC2, transcriptional silencing of a sequence of approximately 40 kb in another locus HOXD, thereby regulating staining quality and transcription, further affecting the expression of proliferating and differentiated genes. The remote regulation mechanism of lncRNA is widespread in organisms, and more than 20% of LncRNAs can function by binding to PRC2 or other similar complexes. LncRNA plays an important role in the growth and development of imprinted genes. Less than 5% of the imprinted genes in the human genome play a key regulatory role in embryonic development, fetal growth and postnatal growth. Various LncRNAs such as H19 are involved in gene imprinting. LncRNA H19 is a miRNA-675 precursor with high levels of H19 transcription in embryonic tissues, which is expressed in maternal origin and down-regulated after birth. During embryonic development, the expression patterns of these two genes are similar and co-regulated in the same tissue at the same developmental stage. IGF2 is highly conserved in vertebrates is an important growth factor. In most embryonic tissues, H19 and IGF2 exhibit single allele expression, and there is an imprinted control region between them. On the maternal chromosome, H19 binds to the transcription factor CTCF, blocking the binding of downstream enhancers to IGF2. Promotes the expression of H19; on the paternal chromosome, the downstream enhancer binds only to the IGF2 promoter but not to the H19 promoter, promotes IGF2 expression, inhibits H19 expression, H19 has bidirectional regulation. In the mouse model of teratoma, the phenomenon that the embryo grows too fast is found, indicating that H19 has a tumor-suppressing effect. The lncRNA gene xist has a similar mechanism to HOTAIR and can recruit and bind PRC2 to mediate gene silencing. Mammalian X chromosome inactivation is mediated by a 17 kb lncRNA-Xist cis-acting. The X inactivation center (Xic) controls the silencing of one of the two X chromosomes to maintain the compensation effect. RepA plays a key role in the regulation of X chromosome inactivation. RepA (a 1.6 kb fragment on Xist RNA) recruits Polycomb repressive complex 2 (PRC2). If Xist locus is activated, Xist and PRC2 are activated. Extending along the X chromosome, the overexpressed Xist binds more PRC2 through the RepA sequence, causing extensive trimethylation of the X-gram histone H3K27, covering the key sites of the chromosome, causing methylation of the chromosome H3K27. By targeting EZH2, the chromosomes that will be inactivated cause X chromosome reconstitution and inactivation, which in turn regulates gene proliferation and differentiation. Similarly, Tsix is an antisense transcript of Xist. In order to prevent RepA from recruiting PRC2, Tsix competes with RepA for binding to PRC2 and is involved in the regulation of X chromosome inactivation as an antagonist of Xist. The study of livestock lncRNA is in its infancy. Huang et al.screened 449 LncRNAs in 405 intergenic regions by feature analysis using published bovine-specific expression sequence tags. These LncRNAs have a tissue-specific expression in mammals. The non-coding RNA of the chain, through chromosomal localization and secondary structure analysis, found that this lncRNA was up-regulated in porcine fetal skeletal muscle and had a significant effect on the development of porcine fetal skeletal muscle. Li et al.used RNA-seq technology and bioinformatics analysis to identify 281 new LncRNAs in the chicken genome, which are related to chicken skeletal muscle development and less conserved than the coding gene sequence, which is consistent with the results of Huang et al.

Reference

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Loudon M E. The origin and development of malocclusions. When, where and how dental malocclusions develop. Int J Orthod Milwaukee. 2013, 24(1):57-65.

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