Sonic hedgehog controls epaxial muscle determination through Myf5 activation

Development ◽  
1999 ◽  
Vol 126 (18) ◽  
pp. 4053-4063 ◽  
Author(s):  
A.G. Borycki ◽  
B. Brunk ◽  
S. Tajbakhsh ◽  
M. Buckingham ◽  
C. Chiang ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Mouse Embryo ◽  
Body Wall ◽  
Presomitic Mesoderm ◽  
Dorsal Neural Tube ◽  
Body Wall Muscles ◽  
Myogenic Progenitor Cells ◽  
Epaxial Muscle

Sonic hedgehog (Shh), produced by the notochord and floor plate, is proposed to function as an inductive and trophic signal that controls somite and neural tube patterning and differentiation. To investigate Shh functions during somite myogenesis in the mouse embryo, we have analyzed the expression of the myogenic determination genes, Myf5 and MyoD, and other regulatory genes in somites of Shh null embryos and in explants of presomitic mesoderm from wild-type and Myf5 null embryos. Our findings establish that Shh has an essential inductive function in the early activation of the myogenic determination genes, Myf5 and MyoD, in the epaxial somite cells that give rise to the progenitors of the deep back muscles. Shh is not required for the activation of Myf5 and MyoD at any of the other sites of myogenesis in the mouse embryo, including the hypaxial dermomyotomal cells that give rise to the abdominal and body wall muscles, or the myogenic progenitor cells that form the limb and head muscles. Shh also functions in somites to establish and maintain the medio-lateral boundaries of epaxial and hypaxial gene expression. Myf5, and not MyoD, is the target of Shh signaling in the epaxial dermomyotome, as MyoD activation by recombinant Shh protein in presomitic mesoderm explants is defective in Myf5 null embryos. In further support of the inductive function of Shh in epaxial myogenesis, we show that Shh is not essential for the survival or the proliferation of epaxial myogenic progenitors. However, Shh is required specifically for the survival of sclerotomal cells in the ventral somite as well as for the survival of ventral and dorsal neural tube cells. We conclude, therefore, that Shh has multiple functions in the somite, including inductive functions in the activation of Myf5, leading to the determination of epaxial dermomyotomal cells to myogenesis, as well as trophic functions in the maintenance of cell survival in the sclerotome and adjacent neural tube.

scholarly journals Modeling the Body of the Embryo during the Somitic Period

2018 ◽  
Vol 1 (1) ◽  
pp. 57-62
Author(s):  
Mariana Rojas ◽  
Carolina Smok
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Skeletal Muscles ◽  
Body Wall ◽  
Axial Skeleton ◽  
The Body ◽  
Dorsal Neural Tube ◽  
Somite Formation ◽  
Low Threshold ◽  
Muscle Precursor Cells

The somite or phylotypic period is similar in many vertebrate species from fish to man. Somites consist of thickening of the mesoderm, they simultaneously form in pairs, one on each side of the notochord. In the human embryo formation of somites is initiated on day 20, resulting in a total of three pairs of somites per day with a total of 44±2 pairs of somites. Somite formation occurs where the FGF -8 is at a low threshold. Positional somites identity is specified by the combined expression of the Hox gene complex. Somites give rise to axial skeleton (vertebrae and ribs), all skeletal muscles including members of the body wall and also most of the dermis. The WNT protein induces muscle precursor cells from the dorso medial portion of the somite and MIF5 gene expression. The somite dermatome dermis becomes action neurotrofina3 (NT -3) secreted by the dorsal neural tube. Sonic hedgehog protein produced by the notochord and neural tube induces sclerotome formation, from somite ventrally and the expression of PAX 1 which in turn, controls the formation of chondrogenesis and vertebrae.

scholarly journals Noggin acts downstream of Wnt and Sonic Hedgehog to antagonize BMP4 in avian somite patterning

Development ◽  
1997 ◽  
Vol 124 (22) ◽  
pp. 4605-4614 ◽  
Author(s):  
E. Hirsinger ◽  
D. Duprez ◽  
C. Jouve ◽  
P. Malapert ◽  
J. Cooke ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Body Wall ◽  
Ectopic Expression ◽  
Lateral Compartment ◽  
Lateral Plate ◽  
Vertebrate Embryo ◽  
Myogenic Program ◽  
Epaxial Muscle

In the vertebrate embryo, the lateral compartment of the somite gives rise to muscles of the limb and body wall and is patterned in response to lateral-plate-derived BMP4. Activation of the myogenic program distinctive to the medial somite, i.e. relatively immediate development of the epaxial muscle lineage, requires neutralization of this lateral signal. We have analyzed the properties of molecules likely to play a role in opposing lateral somite specification by BMP4. We propose that the BMP4 antagonist Noggin plays an important role in promoting medial somite patterning in vivo. We demonstrate that Noggin expression in the somite is under the control of a neural-tube-derived factor, whose effect can be mimicked experimentally by Wnt1. Wnt1 is appropriately expressed in the neural tube. Furthermore, we show that Sonic Hedgehog is able to activate ectopic expression of Noggin resulting in the blocking of BMP4 specification of the lateral somite. Our results are consistent with a model in which Noggin activation lies downstream of the SHH and Wnt signaling pathways.

scholarly journals Coordinate actions of BMPs, Wnts, Shh and noggin mediate patterning of the dorsal somite

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 3955-3963 ◽  
Author(s):  
C. Marcelle ◽  
M.R. Stark ◽  
M. Bronner-Fraser
Keyword(s):  
Molecular Marker ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Direct Action ◽  
Floor Plate ◽  
Dorsoventral Axis ◽  
Dorsal Neural Tube ◽  
Ventral Neural Tube ◽  
Vertebrate Embryos ◽  
Epaxial Muscle

Shortly after their formation, somites of vertebrate embryos differentiate along the dorsoventral axis into sclerotome, myotome and dermomyotome. The dermomyotome is then patterned along its mediolateral axis into medial, central and lateral compartments, which contain progenitors of epaxial muscle, dermis and hypaxial muscle, respectively. Here, we used Wnt-11 as a molecular marker for the medial compartment of dermomyotome (the ‘medial lip’) to demonstrate that BMP in the dorsal neural tube indirectly induces formation of the medial lip by up-regulating Wnt-1 and Wnt-3a (but not Wnt-4) expression in the neural tube. Noggin in the dorsal somite may inhibit the direct action of BMP on this tissue. Wnt-11 induction is antagonized by Sonic Hedgehog, secreted by the notochord and the floor plate. Together, our results show that the coordinated actions of the dorsal neural tube (via BMP and Wnts), the ventral neural tube/notochord (via Shh) and the somite itself (via noggin) mediates patterning of the dorsal compartment of the somite.

scholarly journals Effects of Shh and Noggin on neural crest formation demonstrate that BMP is required in the neural tube but not ectoderm

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 4919-4930 ◽  
Author(s):  
M.A. Selleck ◽  
M.I. Garcia-Castro ◽  
K.B. Artinger ◽  
M. Bronner-Fraser
Keyword(s):  
Neural Crest ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Neural Crest Cells ◽  
Neural Plate ◽  
Bmp Signaling ◽  
Neural Tube Closure ◽  
Dorsal Neural Tube ◽  
Neural Ectoderm ◽  
Tube Closure

To define the timing of neural crest formation, we challenged the fate of presumptive neural crest cells by grafting notochords, Sonic Hedgehog- (Shh) or Noggin-secreting cells at different stages of neurulation in chick embryos. Notochords or Shh-secreting cells are able to prevent neural crest formation at open neural plate levels, as assayed by DiI-labeling and expression of the transcription factor, Slug, suggesting that neural crest cells are not committed to their fate at this time. In contrast, the BMP signaling antagonist, Noggin, does not repress neural crest formation at the open neural plate stage, but does so if injected into the lumen of the closing neural tube. The period of Noggin sensitivity corresponds to the time when BMPs are expressed in the dorsal neural tube but are down-regulated in the non-neural ectoderm. To confirm the timing of neural crest formation, Shh or Noggin were added to neural folds at defined times in culture. Shh inhibits neural crest production at early stages (0-5 hours in culture), whereas Noggin exerts an effect on neural crest production only later (5-10 hours in culture). Our results suggest three phases of neurulation that relate to neural crest formation: (1) an initial BMP-independent phase that can be prevented by Shh-mediated signals from the notochord; (2) an intermediate BMP-dependent phase around the time of neural tube closure, when BMP-4 is expressed in the dorsal neural tube; and (3) a later pre-migratory phase which is refractory to exogenous Shh and Noggin.

Sonic hedgehog is required for survival of both myogenic and chondrogenic somitic lineages

Development ◽  
1998 ◽  
Vol 125 (11) ◽  
pp. 2019-2030 ◽  
Author(s):  
M. Teillet ◽  
Y. Watanabe ◽  
P. Jeffs ◽  
D. Duprez ◽  
F. Lapointe ◽  
...  
Keyword(s):  
Cell Death ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Surgical Ablation ◽  
Cell Lineages ◽  
Ventral Neural Tube ◽  
Close Relationship ◽  
Body Wall Muscles ◽  
Epaxial Muscles ◽  
Axial Organs

In vertebrates, the medial moieties of the somites give rise to the vertebrae and epaxial muscles, which develop in close relationship with the axial organs, neural tube and notochord. The lateral moieties contribute to the ribs and to limb and body wall muscles (hypaxial muscles) after a phase of lateral and ventral migration. Surgical ablation of the neural tube and notochord in the chick embryo during segmentation and early differentiation of the somites (day 2 of incubation) does not affect primary development of the hypaxial muscles, but leads to a complete absence of epaxial muscles, vertebrae and ribs, due to cell death in the somites. Here we demonstrate that cell death, which occurs within 24 hours of excision of the axial organs, affects both myogenic and chondrogenic cell lineages defined, respectively, by the expression of MyoD and Pax-1 genes. In contrast, Pax-3 transcripts, normally present in cells giving rise to hypaxial muscles, are preserved in the excised embryos. Backgrafting either the ventral neural tube or the notochord allows survival of MyoD- and Pax-1-expressing cells. Similarly, Sonic hedgehog-producing cells grafted in place of axial organs also rescue MyoD- and Pax-1-expressing cells from death and allow epaxial muscles, ribs and vertebrae to undergo organogenesis. These results demonstrate that the ventral neural tube and the notochord promote the survival of both myogenic and chondrogenic cell lineages in the somites and that this action is mediated by Sonic hedgehog.

Pax3 functions in cell survival and in pax7 regulation

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1665-1674 ◽  
Author(s):  
A.G. Borycki ◽  
J. Li ◽  
F. Jin ◽  
C.P. Emerson ◽  
J.A. Epstein
Keyword(s):  
Cell Survival ◽  
Neural Tube ◽  
Muscle Development ◽  
Paraxial Mesoderm ◽  
Wild Type ◽  
Presomitic Mesoderm ◽  
Surface Ectoderm ◽  
Dorsal Neural Tube ◽  
Vertebrate Embryos ◽  
Somitic Mesoderm

In developing vertebrate embryos, Pax3 is expressed in the neural tube and in the paraxial mesoderm that gives rise to skeletal muscles. Pax3 mutants develop muscular and neural tube defects; furthermore, Pax3 is essential for the proper activation of the myogenic determination factor gene, MyoD, during early muscle development and PAX3 chromosomal translocations result in muscle tumors, providing evidence that Pax3 has diverse functions in myogenesis. To investigate the specific functions of Pax3 in development, we have examined cell survival and gene expression in presomitic mesoderm, somites and neural tube of developing wild-type and Pax3 mutant (Splotch) mouse embryos. Disruption of Pax3 expression by antisense oligonucleotides significantly impairs MyoD activation by signals from neural tube/notochord and surface ectoderm in cultured presomitic mesoderm (PSM), and is accompanied by a marked increase in programmed cell death. In Pax3 mutant (Splotch) embryos, MyoD is activated normally in the hypaxial somite, but MyoD-expressing cells are disorganized and apoptosis is prevalent in newly formed somites, but not in the neural tube or mature somites. In neural tube and somite regions where cell survival is maintained, the closely related Pax7 gene is upregulated, and its expression becomes expanded into the dorsal neural tube and somites, where Pax3 would normally be expressed. These results establish that Pax3 has complementary functions in MyoD activation and inhibition of apoptosis in the somitic mesoderm and in repression of Pax7 during neural tube and somite development.

Severe defects in the formation of epaxial musculature in open brain (opb) mutant mouse embryos

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 79-86 ◽  
Author(s):  
R. Sporle ◽  
T. Gunther ◽  
M. Struwe ◽  
K. Schughart
Keyword(s):  
Neural Tube ◽  
Body Wall ◽  
Mutant Mouse ◽  
Expression Patterns ◽  
Mouse Embryos ◽  
Surface Ectoderm ◽  
Altered Expression ◽  
Dorsal Neural Tube ◽  
Mutant Mouse Embryos ◽  
Derivatives Of

The differentiation of somite derivatives is dependent on signals from neighboring axial structures. While ventral signals have been described extensively, little is known about dorsal influences, especially those from the dorsal half of the neural tube. Here, we describe severe phenotypic alterations in dorsal somite derivatives of homozygous open brain (opb) mutant mouse embryos which suggest crucial interactions between dorsal neural tube and dorsal somite regions. At Theiler stage 17 (day 10.5 post coitum) of development, strongly altered expression patterns of Pax3 and Myf5 were observed in dorsal somite regions indicating that the dorsal myotome and dermomyotome were not differentiating properly. These abnormalities were later followed by the absence of epaxial (dorsal) musculature; whereas, body wall and limb musculature formed normally. Analysis of Mox1 and Pax1 expression in opb embryos revealed additional defects in the differentiation of the dorsal sclerotome. The observed abnormalities coincided with defects in differentiation of dorsal neural tube regions. The implications of our findings for interactions between dorsal neural tube, surface ectoderm and dorsomedial somite regions in specifying epaxial musculature are discussed.

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