2014 Group Project 8

2014 Student Projects
2014 Student Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7 | Group 8
The Group assessment for 2014 will be an online project on Fetal Development of a specific System. This page is an undergraduate science embryology student and may contain inaccuracies in either description or acknowledgements.

Musculoskeletal

--Mark Hill (talk) 15:21, 26 August 2014 (EST) OK you have nothing here, not even a project title (that I added). I will be asking your group questions in the lab tomorrow. How about some content, references, sources for each section. See Lab 3 Assessment.

This webpage will be focusing on fetal muscular development.

Making Gains

For all you big boys out there who want to get jacked this is where it all starts in 2 easy steps. To be expanded upon...THIS IS NOT BROSCIENCE

Muscle development General Timeline

Primary myofibers develop in first trimester, Secondary myofibers develop during Second and Third Trimester We should do a brief overview of primary myofiber formation, and extensive overview of secondary myofiber formation)

Background Embryonic development

Mesenchymal progenitor cells from somites(occiptal, cervical, thoracic, lumbar, sacral), undergo multiple differentiation stages to create muscle fibers.

http://www.mdconsult.com/books/figure.do?figure=true&eid=4-u1.0-B978-1-4377-2002-0..00015-1--f0025&sectionEid=4-u1.0-B978-1-4377-2002-0..00015-1&isbn=978-1-4377-2002-0&uniqId=464007141-2 (demonstration of myotomes in week 6 and 8)

Skeletal muscle Muscle develops from a process known as myogenesis. Mesenchymal cells differentiates into embryonic muscle cells, myoblasts. Myoblasts fuse and elongate to form myotubes which are multinucleated and cylindrical.

The neural tube and notochord release signaling molecules like Shh, Wnts and [BMP]-4. These signaling molecules act on transcription factors of the MyoD family and Pax .The MyoD or MrF family includes MyoD, Myf-5 , myogenin and Myrf4 . The MyoD family of transcription factors, like MyoD are myogenic bHLH (basic helix loop helix) transcription factors. Pax-3 and the MyoD induce myogenesis, formation of myoblasts. Pax-3 also acts on c-met which is a migratory peptide. Skeletal muscle is derived from the somites. Paraxial mesoderm segments into somite structures on both sides of the notochord and neural tube. Somites are mesodermal structures where the dorsal most end of the somite, which is known as the dermomyotome, becomes skeletal muscle and dermis . A small anterior portion of the paraxial mesoderm remains un-segmented and eventually forms some muscles of the head .

The myotome lies in-between the scleratome which is ventrally located. The scleratome forms the cartilage and bone of the axial skeleton of the embryo. The dermomyotome is located dorsally and forms the first skeletal muscle in the embryo. The medial part of the dermomyotome forms the dorsal and intecostal muscles whilst the lateral part of the dermomyotome forms the limb and ventral muscles .

Myogenesis occurs in two phases; primary and secondary which occur in embryonic and fetal periods Primary myotubes express MHC slow myosin heavy chains . The primary myotubes form the structure and scaffold upon which secondary myotubes form during secondary myogenesis which occurs in the fetal period .

Molecular and Cellular regulation of fetal myogenesis

Skeletal myofiber number is set at birth . This was found using experiments on mice and pigs. Similar trends have been observed in humans as found by Widdowson et al (1972) where a huge increase and then levelling of gastrocnemius myofibers were found in the gestational period .

Skeletal muscle development Multipotent mesenchymal cells (MSC) form myoblasts as well as adipocytes and fibroblasts . Therefore specific the nutrients and growth are important in directing the growth of these MSC into either adipocytes or myoblasts . Myoblasts differentiate form the embryonic, fetal and adult skeletal muscle and in fact myoblasts differentiate to form either three early on. Myoblasts fuse and form primary myoblast or myotubes. As discussed previously the primary myotubes form the scaffolding for which the fetal myoblasts will differentiate into secondary myotubes and add too . There are a greater deal of secondary myofibers than primary and are receptive to nutrients and growth factors. Muscle regulatory factors (MRFs) control the proliferation of secondary myoblasts. MRF’s are helix-loop-helix transcription factors. Myoblasts early on express PAX7 and MYF5. PAX7 and MYF5 act on regulatory proteins of the cell cycle like CDK4 and Cyclin D1. CDK4 and Cyclin D1 dephosphorylate RB. RB when phosphorylated is active and inhibits the cell-cell progression in the cell cycle and hence inhibits proliferation. Therefore Cyclin and CDK4 in this case induces cell proliferation. ; , These creates more fetal myoblasts committed which are committed or programmed to form fetal or secondary myofibers later on. These committed myoblasts express MRF, MYOD. MYOD acts on myostatin to take the myoblast out of the cell cycle and stop it from proliferating ; .Now the myoblast is ready for differentiation. The phosphorylation of RB at this period helps to slow the activity of the cell cycle. The myoblasts differentiate and fuse to become multinucleated myotubes as discussed previously. In the formed myotubes MRFs like Myogenin and MRF4 act to inhibit cell cycle and proliferation by acting regulatory proteins like P21 to stop the cell cycle ; This allows the conversion of the myotube into a myofiber. The myofiber can express desmin an intermediate filament that is increasingly seen as gestation progresses. Growth factors, amino acids and stretch/load activity act on myofibers to affect subsequent hypertrophy maturation of myofibers

Myofiber hypertrophy is occurs when protein synthesis is greater than protein degradation. The resulting accumulation of protein results in hypertrophy. Therefore maintaining protein levels is important in the hypertrophy of myofibers. This is regulated by nutrients and growth factors (GFs). Growth factors There are a large number of growth factors that affect fetal myogenesis. Some of the main GFs as Brown (2014) describes in her article “IGF1, insulin, basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF- β)” ; , . Experiments have shown that if IGF1 is removed reduced muscle mass and hypoplasia has resulted. And increased IFG1 expression has resulted in hyperplasia and increased skeletal muscle. IFG1 has also been found to enhance protein synthesis. ; , . Insulin similarly has been found to promote fetal muscle growth and protein synthesis. Basic fibroblast growth factor (bFGF) and transforming growth factor-β (TGF- β) induce proliferation and myogenesis by upregulating cyclin D.

Nutrients Being the building block of proteins, amino acids are important in muscle protein synthesis. But they are more important in adult muscle protein synthesis than fetal muscle protein synthesis. Experiments have shown for example an amino acid infusion did not always result in a fetal muscle growth, only when there was a rise in the insulin levels. And little is known of the interaction of amino acids and growth factors in the context of fetal myogenesis. Research has shown that fetal or secondary myofibers are more prone to suffer from nutrient deficiency than primary myofibers in pigs and sheep. , , .

Fetal myofiber number have been observed to decrease with detal nutrient deficiency. This is concerning as myofiber numbers are set at birth. Nutrients are also important for fetal myofiber hypertrophy. Stretch and loading Stretch and loading also affect hypertrophy. .

Tendon Development

Tendons are connective tissue which join muscle and bone allowing the transmission of force. Tendons primary embryonic structure originate from mesenchymal progenitor somite cells with further contributions of Neural Crest and Lateral plate mesoderm.

Appearance of tendons begins in the 20th Carnegie stage and marks the beginning of fibrillogenesis. This process is initiated by fibroblasts in series of extracellular compartments; they enlarge the cells domain into extracellular space. Channels deep in the cytoplasm drive the process of elongation, these channels location is associated with Golgi bodies.

First type of compartments are formed by collagen containing secretory vacuoles which fuse with surrounding cell membranes. Initial fibrillogenesis is mediated my macromolecular interactions based on vacuole content, with a lesser input from receptor membrane interactions. Fibril groups as fibres close to the cell surface and Secondary extracellular compartments form; at this stage fibroblast are arranged adjacently. Third level of compartmentalization forms later when fibroblast are adjacent with 2 or more other fibroblasts. As the tendon matures fibres coalesce invading each other with interdigitating processes. Secretory vacuole persist, laterally aggregating with further growth preserving sites for fibril deposit. Collagen fiber assembly branch creating fibre networks along fascicles. Fibres branch within tendon fascicle

The main regulatory factors of tendon fibrillogenesis are Leucine-rich repeat proteoglycans. Fibromodulin; a keratin sulphate present in most tissue Decorin; a chondroitin sulphate strongly expressed in tendon growth Lumician; a keratin sulphate, key for development of cornea stroma, limited impact on extracellular glycoprotein matices.

Second Trimester Muscular development

Cranial muscles originate from head mesoderm

1st Arch Muscles for Mastication:

2nd Arch Muscles for Facial Expression:

3rd Arch: Stylopharyngeus

4th Arch: Levator Palatini, Intrinsic Muscles of Larynx and Pharynx

Myotomes from Somites (From lect) C3,4,5: supply the diaphragm for breathing. C5: supply shoulder muscles and muscles to bend our elbow. C6: for bending the wrist back. C7: for straightening the elbow. C8: bends the fingers. T1: spreads the fingers. T1-T12: supplies the chest wall and abdominal muscles. L2: bends the hip. L3: straightens the knee. L4: pulls the foot up. L5: wiggles the toes. S1: pulls the foot down. S3,4,5: supply the bladder, bowel, sex organs, anal and other pelvic muscles.

NeoNatal

Not all embryonic muscle fibers persist; many of them fail to establish themselves as necessary units of the muscle and soon degenerate. (Moore: The Developing Human, 9th ed.)

Mechanism/Structure of Muscle fibers

Muscle Fiber types

slow twitch (Type I) fast twitch (Type IIa) fast twitch (Type IIb)

For fiber types I think we should only do that of the skeletal muscle fiber types since cardiac and smooth muscle are not part of the musculo-skeletal system

Abnormalities

Duchenne Muscular Dystrophy(DMD)

Caused by a mutation of the dystrophin protein on locus Xp21; this protein complex connects the cytoskeleton of muscle fibres to the extracellular matrix. Abnormal dystrophin results in a degradation of cellular integrity, excessive penetration of sarcolemma by calcium and water entering mitochondria increasing pressure and bursting. The lack of significant load during fetal development results in minimal wasting, it is detected in postnatal babies at 3-5 years old with muscles resisting gravity being the first to waste. Patients are restricted to wheelchairs by their early teens and have a life expectancy of 25 years. The incidence in male infants is 1 in 36,000.

Typically males are affected while females are carriers. In the offspring of a carrier mother and unaffected father; sons have 50% chance of affected and daughter’s 50% chance of becoming carriers. Since the disease is a terminal illness killing in mid-twenties; affected fathers are not considered in the situation. Absence of affected fathers means it is very unlikely for daughters to be affected.

Types of Muscular Dystrophy; Duchenne Muscular Dystrophy, Becker type muscular Dystrophy, Occulophayngeal muscular Dystrophy,

Absence of specific muscles;

References

Anatomy and variations of palmaris longus in fetuses.

Development of the rectus abdominis and its sheath in the human fetus.

Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity.

The normal growth of the biceps brachii muscle in human fetuses.

References to format in later

Biggar, W. (2006). Duchenne muscular dystrophy. Pediatrics in Review, 27(3), pp.83--88.

Birk, D. and Trelstad, R. (1986). Extracellular compartments in tendon morphogenesis: collagen fibril, bundle, and macroaggregate formation. The Journal of cell biology, 103(1), pp.231--240.

Deries, M., Gon\ccalves, A., Vaz, R., Martins, G., Rodrigues, G. and Thorsteinsd\'ottir, S. (2012). Extracellular matrix remodeling accompanies axial muscle development and morphogenesis in the mouse.Developmental Dynamics, 241(2), pp.350--364.

Dom\`enech-Mateu, J., Mart\'\inez-Pozo, A. and Arn\'o-Palau, A. (1994). Development of the tendon of todaro during the human embryonic and fetal periods. The Anatomical Record, 238(3), pp.374--382. Harel, I., Maezawa, Y., Avraham, R., Rinon, A., Ma, H., Cross, J., Leviatan, N., Hegesh, J., Roy, A., Jacob-Hirsch, J. and others, (2012). Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis. Proceedings of the National Academy of Sciences, 109(46), pp.18839--18844.

Herchenhan, A., Bayer, M., Svensson, R., Magnusson, S. and Kj\aer, M. (2013). In vitro tendon tissue development from human fibroblasts demonstrates collagen fibril diameter growth associated with a rise in mechanical strength. Developmental Dynamics, 242(1), pp.2--8.

Hoffman, E., Brown Jr, R. and Kunkel, L. (1987). Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell, 51(6), pp.919--928.

Katori, Y., Hyun Kim, J., Rodr\'\iguez-V\'azquez, J., Kawase, T., Murakami, G. and Hwan Cho, B. (2011). Early fetal development of the intermediate tendon of the human digastricus and omohyoideus muscles: a critical difference in histogenesis. Clinical Anatomy, 24(7), pp.843--852.

KINMONT, P. (2008). development of the human achilles tendon enthesis organ. Journal of Anatomy.

Nichol, P., Corliss, R., Yamada, S., Shiota, K. and Saijoh, Y. (2012). Muscle Patterning in Mouse and Human Abdominal Wall Development and Omphalocele Specimens of Humans. The Anatomical Record, 295(12), pp.2129--2140.

Rodriguez-Guzman, M., Montero, J., Santesteban, E., Ga\~nan, Y., Macias, D. and Hurle, J. (2007). Tendon-muscle crosstalk controls muscle bellies morphogenesis, which is mediated by cell death and retinoic acid signaling. Developmental biology, 302(1), pp.267--280.

Rodr\'\iguez-V\'azquez, J., M\'erida-Velasco, J. and Verdugo-L\'opez, S. (2010). Development of the Stapedius Muscle and Unilateral Agenesia of the Tendon of the Stapedius Muscle in a Human Fetus. The anatomical record, 293(1), pp.25--31.

Shwartz, Y., Farkas, Z., Stern, T., Asz\'odi, A. and Zelzer, E. (2012). Muscle contraction controls skeletal morphogenesis through regulation of chondrocyte convergent extension. Developmental biology, 370(1), pp.154--163.

Sussman, M. (2002). Duchenne muscular dystrophy. Journal of the American Academy of Orthopaedic Surgeons, 10(2), pp.138--151.

Tich\`y, M. (1989). The morphogenesis of human sphincter urethrae muscle. Anatomy and embryology, 180(6), pp.577--582.

Tich\`y, M. and Grim, M. (1985). Morphogenesis of the human gluteus maximus muscle arising from two muscle primordia. Anatomy and embryology, 173(2), pp.275--277.

Yiu, E., Kornberg, A. and others, (2008). Duchenne muscular dystrophy. Neurology India, 56(3), p.236.

Zagrebin, A. (1971). Morphogenesis of the lamellar receptors of human striated muscle.Bulletin of Experimental Biology and Medicine, 71(2), pp.199--201.

Abnormalities

1 Scoliosis 2. Duchenne Muscular Dystrophy 3. Syndactyly : split-hand malformation

R Geoffrey Burwell, Peter H Dangerfield, Alan Moulton and Theodoros B Grivas. (2011). Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network . Scoliosis. 6 (6), p1-26

(links: http://www.scoliosisjournal.com/content/6/1/26)

Patrizia Pessina, Daniel Cabrera, María Gabriela Morales, Cecilia A Riquelme, Jaime Gutiérrez, Antonio L Serrano, Enrique Brandan and Pura Muñoz-Cánoves. (2014). Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy. Skeletal Muscle. 4 (7), p1-17

(links: http://www.skeletalmusclejournal.com/content/4/1/7)

Naeimeh Tayebi, Aleksander Jamsheer34, Ricarda Flöttmann1, Anna Sowinska-Seidler, Sandra C Doelken. (2014). Deletions of exons with regulatory activity at the DYNC1I1 locus are associated with split-hand/split-foot malformation: array CGH screening of 134 unrelated families. Orphanet Journal of Rare Disease. 9 (108), p1-9

(links: http://www.ojrd.com/content/9/1/108)

References

To be properly referenced at a later date

http://www.journalofanimalscience.org/content/89/2/583.full

http://www.jgenomics.com/v01p0029.htm

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