MyoD and Myf-5 define the specification of musculature of distinct embryonic origin

1998 ◽  
Vol 76 (6) ◽  
pp. 1079-1091 ◽  
Author(s):  
Boris Kablar ◽  
Atsushi Asakura ◽  
Kirsten Krastel ◽  
Chuyan Ying ◽  
Linda L May ◽  
...  

Mounting evidence supports the notion that Myf-5 and MyoD play unique roles in the development of epaxial (originating in the dorso-medial half of the somite, e.g. back muscles) and hypaxial (originating in the ventro-lateral half of the somite, e.g. limb and body wall muscles) musculature. To further understand how Myf-5 and MyoD genes co-operate during skeletal muscle specification, we examined and compared the expression pattern of MyoD-lacZ (258/-2.5lacZ and MD6.0-lacZ) transgenes in wild-type, Myf-5, and MyoD mutant embryos. We found that the delayed onset of muscle differentiation in the branchial arches, tongue, limbs, and diaphragm of MyoD-/- embryos was a consequence of a reduced ability of myogenic precursor cells to progress through their normal developmental program and not because of a defect in migration of muscle progenitor cells into these regions. We also found that myogenic precursor cells for back, intercostal, and abdominal wall musculature in Myf-5-/-embryos failed to undergo normal translocation or differentiation. By contrast, the myogenic precursors of intercostal and abdominal wall musculature in MyoD-/- embryos underwent normal translocation but failed to undergo timely differentiation. In conclusion, these observations strongly support the hypothesis that Myf-5 plays a unique role in the development of muscles arising after translocation of epithelial dermamyotome cells along the medial edge of the somite to the subjacent myotome (e.g., back or epaxial muscle) and that MyoD plays a unique role in the development of muscles arising from migratory precursor cells (e.g., limb and branchial arch muscles, tongue, and diaphragm). In addition, the expression pattern of MyoD-lacZ transgenes in the intercostal and abdominal wall muscles of Myf-5-/- and MyoD-/- embryos suggests that appropriate development of these muscles is dependent on both genes and, therefore, these muscles have a dual embryonic origin (epaxial and hypaxial).Key words: epaxial and hypaxial muscle, Myf-5, MyoD, mouse development, somite.

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 329-344 ◽  
Author(s):  
T.F. Schilling ◽  
T. Piotrowski ◽  
H. Grandel ◽  
M. Brand ◽  
C.P. Heisenberg ◽  
...  

Jaws and branchial arches together are a basic, segmented feature of the vertebrate head. Seven arches develop in the zebrafish embryo (Danio rerio), derived largely from neural crest cells that form the cartilaginous skeleton. In this and the following paper we describe the phenotypes of 109 arch mutants, focusing here on three classes that affect the posterior pharyngeal arches, including the hyoid and five gill-bearing arches. In lockjaw, the hyoid arch is strongly reduced and subsets of branchial arches do not develop. Mutants of a large second class, designated the flathead group, lack several adjacent branchial arches and their associated cartilages. Five alleles at the flathead locus all lead to larvae that lack arches 4–6. Among 34 other flathead group members complementation tests are incomplete, but at least six unique phenotypes can be distinguished. These all delete continuous stretches of adjacent branchial arches and unpaired cartilages in the ventral midline. Many show cell death in the midbrain, from which some neural crest precursors of the arches originate. lockjaw and a few mutants in the flathead group, including pistachio, affect both jaw cartilage and pigmentation, reflecting essential functions of these genes in at least two neural crest lineages. Mutants of a third class, including boxer, dackel and pincher, affect pectoral fins and axonal trajectories in the brain, as well as the arches. Their skeletal phenotypes suggest that they disrupt cartilage morphogenesis in all arches. Our results suggest that there are sets of genes that: (1) specify neural crest cells in groups of adjacent head segments, and (2) function in common genetic pathways in a variety of tissues including the brain, pectoral fins and pigment cells as well as pharyngeal arches.


Development ◽  
2000 ◽  
Vol 127 (8) ◽  
pp. 1751-1766 ◽  
Author(s):  
A. Caton ◽  
A. Hacker ◽  
A. Naeem ◽  
J. Livet ◽  
F. Maina ◽  
...  

During development, cranial motor neurons extend their axons along distinct pathways into the periphery. For example, branchiomotor axons extend dorsally to leave the hindbrain via large dorsal exit points. They then grow in association with sensory ganglia, to their targets, the muscles of the branchial arches. We have investigated the possibility that pathway tissues might secrete diffusible chemorepellents or chemoattractants that guide cranial motor axons, using co-cultures in collagen gels. We found that explants of dorsal neural tube or hindbrain roof plate chemorepelled cranial motor axons, while explants of cranial sensory ganglia were weakly chemoattractive. Explants of branchial arch mesenchyme were strongly growth-promoting and chemoattractive for cranial motor axons. Enhanced and oriented axon outgrowth was also elicited by beads loaded with Hepatocyte Growth Factor (HGF); antibodies to this protein largely blocked the outgrowth and orientation effects of the branchial arch on motor axons. HGF was expressed in the branchial arches, whilst Met, which encodes an HGF receptor, was expressed by subpopulations of cranial motor neurons. Mice with targetted disruptions of HGF or Met showed defects in the navigation of hypoglossal motor axons into the branchial region. Branchial arch tissue may thus act as a target-derived factor that guides motor axons during development. This influence is likely to be mediated partly by Hepatocyte Growth Factor, although a component of branchial arch-mediated growth promotion and chemoattraction was not blocked by anti-HGF antibodies.


Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4133-4141 ◽  
Author(s):  
H. Kato ◽  
Y. Taniguchi ◽  
H. Kurooka ◽  
S. Minoguchi ◽  
T. Sakai ◽  
...  

Notch is involved in the cell fate determination of many cell lineages. The intracellular region (RAMIC) of Notch1 transactivates genes by interaction with a DNA binding protein RBP-J. We have compared the activities of mouse RAMIC and its derivatives in transactivation and differentiation suppression of myogenic precursor cells. RAMIC comprises two separate domains, IC for transactivation and RAM for RBP-J binding. Although the physical interaction of IC with RBP-J was much weaker than with RAM, transactivation activity of IC was shown to involve RBP-J by using an RBP-J null mutant cell line. IC showed differentiation suppression activity that was generally comparable to its transactivation activity. The RBP-J-VP16 fusion protein, which has strong transactivation activity, also suppressed myogenesis of C2C12. The RAM domain, which has no other activities than binding to RBP-J, synergistically stimulated transactivation activity of IC to the level of RAMIC. The RAM domain was proposed to compete with a putative co-repressor for binding to RBP-J because the RAM domain can also stimulate the activity of RBP-J-VP16. These results taken together, indicate that differentiation suppression of myogenic precursor cells by Notch signalling is due to transactivation of genes carrying RBP-J binding motifs.


2019 ◽  
Vol 1 (1) ◽  
pp. 01-05
Author(s):  
Stalin Reddy Challa ◽  
Swathi Goli

Degenerative muscle diseases affect muscle tissue integrity and function. Human embryonic stem cells (hESC) are an attractive source of cells to use in regenerative therapies due to their unlimited capacity to divide and ability to specialize into a wide variety of cell types. A practical way to derive therapeutic myogenic stem cells from hESC is lacking. In this study, we demonstrate the development of two serum-free conditions to direct the differentiation of hESC towards a myogenic precursor state. Using TGFß and PI3Kinase inhibitors in combination with bFGF we showed that one week of differentiation is sufficient for hESC to specialize into PAX3+/PAX7+ myogenic precursor cells. These cells also possess the capacity to further differentiate in vitro into more specialized myogenic cells that express MYOD, Myogenin, Desmin and MYHC, and showed engraftment in vivo upon transplantation in immunodeficient mice. Ex vivo myomechanical studies of dystrophic mouse hindlimb muscle showed functional improvement one month post-transplantation. In summary, this study describes a promising system to derive engrafting muscle precursor cells solely using chemical substances in serum-free conditions and without genetic manipulation.


Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2587-2597 ◽  
Author(s):  
B. Kanzler ◽  
S.J. Kuschert ◽  
Y.H. Liu ◽  
M. Mallo

In Hoxa-2(−/−)embryos, the normal skeletal elements of the second branchial arch are replaced by a duplicated set of first arch elements. We show here that Hoxa-2 directs proper skeletal formation in the second arch by preventing chondrogenesis and intramembranous ossification. In normal embryos, Hoxa-2 is expressed throughout the second arch mesenchyme, but is excluded from the chondrogenic condensations. In the absence of Hoxa-2, chondrogenesis is activated ectopically within the rostral Hoxa-2 expression domain to form the mutant set of cartilages. In Hoxa-2(−/−)embryos the Sox9 expression domain is shifted into the normal Hoxa-2 domain. Misexpression of Sox9 in this area produces a phenotype resembling that of the Hoxa-2 mutants. These results indicate that Hoxa-2 acts at early stages of the chondrogenic pathway, upstream of Sox9 induction. We also show that Hoxa-2 inhibits dermal bone formation when misexpressed in its precursors. Furthermore, molecular analyses indicate that Cbfa1 is upregulated in the second branchial arches of Hoxa-2 mutant embryos suggesting that prevention of Cbfa1 induction might mediate Hoxa-2 inhibition of dermal bone formation during normal second arch development. The implications of these results on the patterning of the branchial area are discussed.


Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 437-445 ◽  
Author(s):  
H. Brohmann ◽  
K. Jagla ◽  
C. Birchmeier

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.


Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 743-752 ◽  
Author(s):  
M. Kruger ◽  
D. Mennerich ◽  
S. Fees ◽  
R. Schafer ◽  
S. Mundlos ◽  
...  

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.


Author(s):  
Martin E. Atkinson

Embryology and development have been covered after the main anatomical descriptions in the previous sections, but it is going to precede them in this section. The reason for this departure is that the embryonic development of the head and neck explains much of the mature anatomy which can seem illogical without its developmental history. The development of the head, face, and neck is an area of embryology where significant strides in our understanding have been made in the last few years. The development of the head is intimately related to the development of the brain outlined in Chapter 19 and its effects on shaping the head will be described in Chapters 32 and 33. The major thrust of this chapter is the description of the formation of structures called the pharyngeal (or branchial) arches and the fate of the tissues that contribute to them. All four embryonic germ layers contribute to the pharyngeal arches and their derivatives, hence to further development of the head and neck. Figure 21.1 is a cross section through the neck region of a 3-week old embryo after neurulation and folding described in Chapter 8. It shows the structures and tissues that contribute to the formation of the head and neck: • The neural tube situated posteriorly and the ectomesenchymal neural crest cells that arise as the tube closes; • The paraxial mesoderm anterolateral to the neural tube; • The endodermal foregut tube anteriorly; • The investing layer of ectoderm. The development of all these tissues is intimately interrelated. The pharyngeal arches are very ancient structures in the evolutionary history of vertebrates. The arches and their individual components have undergone many modifications during their long history. In ancestral aquatic vertebrates, as in modern fishes, water was drawn in through the mouth and expelled through a series of gill slits (or branchiae, hence the term ‘branchial arch’) in the sides of the pharynx. Oxygen was extracted as the water was passed over a gill apparatus supported by a branchial arch skeleton moved by branchial muscles controlled by branchial nerves. Although ventilation and respiration is now a function of the lungs in land vertebrates, the pharyngeal arches persist during vertebrate development.


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