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.

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.

Expression of the murine Hoxa4 gene requires both autoregulation and a conserved retinoic acid response element

Development ◽  
1998 ◽  
Vol 125 (11) ◽  
pp. 1991-1998 ◽  
Author(s):  
A.I. Packer ◽  
D.A. Crotty ◽  
V.A. Elwell ◽  
D.J. Wolgemuth
Keyword(s):  
Retinoic Acid ◽  
Reporter Gene ◽  
Neural Tube ◽  
Hox Genes ◽  
Regulatory Region ◽  
Ectopic Expression ◽  
Response Element ◽  
Retinoic Acid Response Element ◽  
Transgenic Embryos

Analysis of the regulatory regions of the Hox genes has revealed a complex array of positive and negative cis-acting elements that control the spatial and temporal pattern of expression of these genes during embryogenesis. In this study we show that normal expression of the murine Hoxa4 gene during development requires both autoregulatory and retinoic acid-dependent modes of regulation. When introduced into a Hoxa4 null background, expression of a lacZ reporter gene driven by the Hoxa4 regulatory region (Hoxa4/lacZ) is either abolished or significantly reduced in all tissues at E10. 5-E12.5. Thus, the observed autoregulation of the Drosophila Deformed gene is conserved in a mouse homolog in vivo, and is reflected in a widespread requirement for positive feedback to maintain Hoxa4 expression. We also identify three potential retinoic acid response elements in the Hoxa4 5′ flanking region, one of which is identical to a well-characterized element flanking the Hoxd4 gene. Administration of retinoic acid to Hoxa4/lacZ transgenic embryos resulted in stage-dependent ectopic expression of the reporter gene in the neural tube and hindbrain. When administered to Hoxa4 null embryos, however, persistent ectopic expression was not observed, suggesting that autoregulation is required for maintenance of the retinoic acid-induced expression. Finally, mutation of the consensus retinoic acid response element eliminated the response of the reporter gene to exogenous retinoic acid, and abolished all embryonic expression in untreated embryos, with the exception of the neural tube and prevertebrae. These data add to the evidence that Hox gene expression is regulated, in part, by endogenous retinoids and autoregulatory loops.

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 Patterning of the chick forebrain anlage by the prechordal plate

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4153-4162 ◽  
Author(s):  
E.M. Pera ◽  
M. Kessel
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Relative Concentration ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Lateral Side ◽  
Expression Domain ◽  
Prechordal Plate ◽  
Chick Forebrain

We analysed the role of the prechordal plate in forebrain development of chick embryos in vivo. After transplantation to uncommitted ectoderm a prechordal plate induces an ectopic, dorsoventrally patterned, forebrain-like vesicle. Grafting laterally under the anterior neural plate causes ventralization of the lateral side of the forebrain, as indicated by a second expression domain of the homeobox gene NKX2.1. Such a lateral ventralization cannot be induced by the secreted factor Sonic Hedgehog alone, as this is only able to distort the ventral forebrain medially. Removal of the prechordal plate does not reduce the rostrocaudal extent of the anterior neural tube, but leads to significant narrowing and cyclopia. Excision of the head process results in the caudal expansion of the NKX2.1 expression in the ventral part of the anterior neural tube, while PAX6 expression in the dorsal part remains unchanged. We suggest that there are three essential steps in early forebrain patterning, which culminate in the ventralization of the forebrain. First, anterior neuralization occurs at the primitive streak stage, when BMP-4-antagonizing factors emanate from the node and spread in a planar fashion to induce anterior neural ectoderm. Second, the anterior translocation of organizer-derived cells shifts the source of neuralizing factors anteriorly, where the relative concentration of BMP-4-antagonists is thus elevated, and the medial part of the prospective forebrain becomes competent to respond to ventralizing factors. Third, the forebrain anlage is ventralized by signals including Sonic Hedgehog, thereby creating a new identity, the prospective hypothalamus, which splits the eye anlage into two lateral domains.

Vitronectin is expressed in the ventral region of the neural tube and promotes the differentiation of motor neurons

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5139-5147 ◽  
Author(s):  
J.R. Martinez-Morales ◽  
J.A. Barbas ◽  
E. Marti ◽  
P. Bovolenta ◽  
D. Edgar ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Sonic Hedgehog ◽  
Motor Neurons ◽  
Neural Tube ◽  
Matrix Protein ◽  
Floor Plate ◽  
Extracellular Matrix Protein ◽  
Neuron Differentiation

The extracellular matrix protein vitronectin and its mRNA are present in the embryonic chick notochord, floor plate and in the ventral neural tube at the time position of motor neuron generation. When added to cultures of neural tube explants of developmental stage 9, vitronectin promotes the generation of motor neurons in the absence of either notochord or exogenously added Sonic hedgehog. Conversely, the neutralisation of endogenous vitronectin with antibodies inhibits over 90% motor neuron differentiation in co-cultured neural tube/notochord explants, neural tube explants cultured in the presence of Sonic hedgehog, and in committed (stage 13) neural tube explants. Furthermore, treatment of embryos with anti-vitronectin antibodies results in a substantial and specific reduction in the number of motor neurons generated in vivo. These results demonstrate that vitronectin stimulates the differentiation of motor neurons in vitro and in vivo. Since the treatment of stage 9 neural tube explants with Sonic hedgehog resulted in induction of vitronectin mRNA expression before the expression of floor plate markers, we conclude that vitronectin may act either as a downstream effector in the signalling cascade induced by Sonic hedgehog, or as a synergistic factor that increases Shh-induced motor neuron differentiation.

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.

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