SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm

Development ◽  
2000 ◽  
Vol 127 (1) ◽  
pp. 109-118 ◽  
Author(s):  
C.S. Lee ◽  
L.A. Buttitta ◽  
N.R. May ◽  
A. Kispert ◽  
C.M. Fan

Dorsoventral polarity of the somitic mesoderm is established by competitive signals originating from adjacent tissues. The ventrally located notochord provides the ventralizing signals to specify the sclerotome, while the dorsally located surface ectoderm and dorsal neural tube provide the dorsalizing signals to specify the dermomyotome. Noggin and SHH-N have been implicated as the ventralizing signals produced by the notochord. Members of the WNT family of proteins, on the other hand, have been implicated as the dorsalizing signals derived from the ectoderm and dorsal neural tube. When presomitic explants are confronted with cells secreting SHH-N and WNT1 simultaneously, competition to specify the sclerotome and dermomyotome domains within the naive mesoderm can be observed. Here, using these explant cultures, we provide evidence that SHH-N competes with WNT1, not only by upregulating its own receptor Ptc1, but also by upregulating Sfrp2 (Secreted frizzled-related protein 2), which encodes a potential WNT antagonist. Among the four known Sfrps, Sfrp2 is the only member expressed in the sclerotome and upregulated by SHH-N recombinant protein. We further show that SFRP2-expressing cells can reduce the dermomyotome-inducing activity of WNT1 and WNT4, but not that of WNT3a. Together, our results support the model that SHH-N at least in part employs SFRP2 to reduce WNT1/4 activity in the somitic mesoderm.

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1665-1674 ◽  
Author(s):  
A.G. Borycki ◽  
J. Li ◽  
F. Jin ◽  
C.P. Emerson ◽  
J.A. Epstein

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.


Development ◽  
1989 ◽  
Vol 106 (1) ◽  
pp. 85-93 ◽  
Author(s):  
C. Kalcheim ◽  
M.A. Teillet

We have investigated dorsal root ganglion formation, in the avian embryo, as a function of the composition of the paraxial somitic mesoderm. Three or four contiguous young somites were unilaterally removed from chick embryos and replaced by multiple cranial or caudal half-somites from quail embryos. Migration of neural crest cells and formation of DRG were subsequently visualized both by the HNK-1 antibody and the Feulgen nuclear stain. At advanced migratory stages (as defined by Teillet et al. Devl Biol. 120, 329–347 1987), neural crest cells apposed to the dorsolateral faces of the neural tube were distributed in a continuous, nonsegmented pattern that was indistinguishable on unoperated sides and on sides into which either half of the somites had been grafted. In contrast, ventrolaterally, neural crest cells were distributed segmentally close to the neural tube and within the cranial part of each normal sclerotome, whereas they displayed a nonsegmental distribution when the graft involved multiple cranial half-somites or were virtually absent when multiple caudal half-somites had been implanted. In spite of the identical dorsal distribution of neural crest cells in all embryos, profound differences in the size and segmentation of DRG were observed during gangliogenesis (E4–9) according to the type of graft that had been performed. Thus when the implant consisted of compound cranial half-somites, giant, coalesced ganglia developed, encompassing the entire length of the graft. On the other hand, very small, dorsally located ganglia with irregular segmentation were seen at the level corresponding to the graft of multiple caudal half-somites. We conclude that normal morphogenesis of dorsal root ganglia depends upon the craniocaudal integrity of the somites.


Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 79-86 ◽  
Author(s):  
R. Sporle ◽  
T. Gunther ◽  
M. Struwe ◽  
K. Schughart

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.


Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3895-3908 ◽  
Author(s):  
S. Dietrich ◽  
F.R. Schubert ◽  
A. Lumsden

The most profound feature of the mature vertebrate somite is its organisation into dorsal dermomyotome, intermediate myotome and ventral sclerotome. We analysed the role of potential signalling structures in this dorsoventral pattern by ablating them or transplanting them to ectopic locations in chick embryos. Our data suggest that the somite represents a naive tissue, entirely depending on external cues for its dorsoventral organisation. Dorsalisation by signals from dorsal neural tube and surface ectoderm stimulates the development of the dermomyotome. Likewise, signals from notochord and floor plate ventralise the somite, at high levels overriding any dorsal information and inducing the sclerotome. The dorsalising factors and lower levels of the ventralising factors act in concert to induce the myotome. Finally, the paraxial mesoderm intrinsically controls its competence to respond to the external inducers.


2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Sakina Rashid ◽  
Grace Kinabo ◽  
Marissa Kellogg ◽  
William P. Howlett ◽  
Marieke C. J. Dekker

Neural tube defects result from failure of neural tube fusion during early embryogenesis, the fourth week after conception. The spectrum of severity is not uniform across the various forms of this congenital anomaly as certain presentations are not compatible with extrauterine life (anencephaly) while, on the other hand, other defects may remain undiagnosed as they are entirely asymptomatic (occult spina bifida). We report a child with previously normal neurological development, a devastating clinical course following superinfection of a subtle spina bifida defect which resulted in a flaccid paralysis below the level of the lesion and permanent neurological deficits following resolution of the acute infection and a back closure surgery.


Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3675-3686 ◽  
Author(s):  
H.M. Stern ◽  
A.M. Brown ◽  
S.D. Hauschka

Previous studies have demonstrated that the neural tube/notochord complex is required for skeletal muscle development within somites. In order to explore the localization of myogenic inducing signals within the neural tube, dorsal or ventral neural tube halves were cultured in contact with single somites or pieces of segmental plate mesoderm. Somites and segmental plates cultured with the dorsal half of the neural tube exhibited 70% and 85% myogenic response rates, as determined by immunostaining for myosin heavy chain. This response was slightly lower than the 100% response to whole neural tube/notochord, but was much greater than the 30% and 10% myogenic response to ventral neural tube with and without notochord. These results demonstrate that the dorsal neural tube emits a potent myogenic inducing signal which accounts for most of the inductive activity of whole neural tube/notochord. However, a role for ventral neural tube/notochord in somite myogenic induction was clearly evident from the larger number of myogenic cells induced when both dorsal neural tube and ventral neural tube/notochord were present. To address the role of a specific dorsal neural tube factor in somite myogenic induction, we tested the ability of Wnt-1-expressing fibroblasts to promote paraxial mesoderm myogenesis in vitro. We found that cells expressing Wnt-1 induced a small number of somite and segmental plate cells to undergo myogenesis. This finding is consistent with the localized dorsal neural tube inductive activity described above, but since the ventral neural tube/notochord also possesses myogenic inductive capacity yet does not express Wnt-1, additional inductive factors are likely involved.


Zygote ◽  
2018 ◽  
Vol 26 (6) ◽  
pp. 457-464 ◽  
Author(s):  
Xiao-tan Zhang ◽  
Guang Wang ◽  
Yan Li ◽  
Manli Chuai ◽  
Kenneth Ka Ho Lee ◽  
...  

SummaryFibroblast growth factor (FGF) signalling acts as one of modulators that control neural crest cell (NCC) migration, but how this is achieved is still unclear. In this study, we investigated the effects of FGF signalling on NCC migration by blocking this process. Constructs that were capable of inducing Sprouty2 (Spry2) or dominant-negative FGFR1 (Dn-FGFR1) expression were transfected into the cells making up the neural tubes. Our results revealed that blocking FGF signalling at stage HH10 (neurulation stage) could enhance NCC migration at both the cranial and trunk levels in the developing embryos. It was established that FGF-mediated NCC migration was not due to altering the expression of N-cadherin in the neural tube. Instead, we determined that cyclin D1 was overexpressed in the cranial and trunk levels when Sprouty2 was upregulated in the dorsal neural tube. These results imply that the cell cycle was a target of FGF signalling through which it regulates NCC migration at the neurulation stage.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shashank Gandhi ◽  
Erica J Hutchins ◽  
Krystyna Maruszko ◽  
Jong H Park ◽  
Matthew Thomson ◽  
...  

During gastrulation, neural crest cells are specified at the neural plate border, as characterized by Pax7 expression. Using single-cell RNA sequencing coupled with high-resolution in situ hybridization to identify novel transcriptional regulators, we show that chromatin remodeler Hmga1 is highly expressed prior to specification and maintained in migrating chick neural crest cells. Temporally controlled CRISPR-Cas9-mediated knockouts uncovered two distinct functions of Hmga1 in neural crest development. At the neural plate border, Hmga1 regulates Pax7-dependent neural crest lineage specification. At premigratory stages, a second role manifests where Hmga1 loss reduces cranial crest emigration from the dorsal neural tube independent of Pax7. Interestingly, this is rescued by stabilized ß-catenin, thus implicating Hmga1 as a canonical Wnt activator. Together, our results show that Hmga1 functions in a bimodal manner during neural crest development to regulate specification at the neural plate border, and subsequent emigration from the neural tube via canonical Wnt signaling.


1992 ◽  
Vol 72 (4) ◽  
pp. 555-567 ◽  
Author(s):  
S. C. Sheppard ◽  
W. G. Evenden

The halide elements are environmentally important and share some common attributes. The heaviest, I, and the lighest, F, are quite toxic and are important industrial pollutants. They are also effectively retained in soils. The others, Cl and Br, can be accumulated to high concentrations in plants, are used in agriculture and are highly mobile in soils. This study investigated the behaviour of the halides in plots, outdoor lysimeters, and laboratory sorption and excised-root experiments. Sorption on soil was ordered as F > I > Br > Cl. Concentrations in plants were generally ordered as CI ≥ Br > > F ≥ I, the inverse of the sorption ordering, as expected. Older tissues, which were also closest to the soil surface, had higher concentrations, and sequestered tissues, such as corn kernels and cabbage heads, had lower concentrations. There was evidence of competitive interaction among the halides and with soil anions such as phosphate and sulfate. This competition reduced the toxicity of I and modified tissue concentrations of the halides, P and S. Another interesting interaction was an increase in Cl and I sorption on soil solids when there were elevated levels or the other halides. Overall, the study of the halides in combination enhanced our understanding of their individual behaviours. Key words: Fluoride, chloride, bromide, iodide, vegetable


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