scholarly journals A Scube2-Shh feedback loop links morphogen release to morphogen signaling to enable scale invariant patterning of the ventral neural tube

2018 ◽  
Author(s):  
Zachary M. Collins ◽  
Kana Ishimatsu ◽  
Tony Y.C. Tsai ◽  
Sean G. Megason
Keyword(s):  
Neural Tube ◽  
Size Reduction ◽  
Morphogen Gradient ◽  
Neural Patterning ◽  
Scale Invariant ◽  
Shh Signaling ◽  
Size Dependent ◽  
Analysis Technique ◽  
Ventral Neural Tube ◽  
Tissue Size

AbstractTo enable robust patterning, morphogen systems should be resistant to variations in gene expression and tissue size. Here we explore how a Shh morphogen gradient in the ventral neural tube enables proportional patterning in embryos of varying sizes. Using a surgical technique to reduce the size of zebrafish embryos and quantitative confocal microscopy, we find that patterning of neural progenitors remains proportional after size reduction. Intriguingly, a protein necessary for Shh release, Scube2, is expressed far from the source of sonic hedgehog production. scube2 expression levels control Shh signaling extent during ventral neural patterning and conversely Shh signaling represses the expression of scube2, thereby restricting its own signaling. scube2 is disproportionately downregulated in size-reduced embryos, providing a potential mechanism for size-dependent regulation of Shh. This regulatory feedback is necessary for pattern scaling, as demonstrated by a loss of scaling in scube2 overexpressing embryos. In a manner akin to the expander-repressor model of morphogen scaling, we conclude that feedback between Shh signaling and scube2 expression enables proportional patterning in the ventral neural tube by encoding a tissue size dependent morphogen signaling gradient.Summary StatementThe Shh morphogen gradient can scale to different size tissues by feedback between Scube2 mediated release of Shh and Shh based inhibition of Scube2 expressionAuthor ContributionsZ.M.C. conducted experiments and data analysis. Z.M.C and S.G.M. conceived the study, designed the experiments, and wrote the paper. K.I and Z.M.C. developed the size reduction technique. T.Y.C.T helped develop the image analysis technique and generated the tg(shha:memCherry) reporter line. S.G.M. supervised the overall study.

Zebrafishsmoothenedfunctions in ventral neural tube specification and axon tract formation

Development ◽  
2001 ◽  
Vol 128 (18) ◽  
pp. 3497-3509 ◽  
Author(s):  
Zoltán M. Varga ◽  
Angel Amores ◽  
Katharine E. Lewis ◽  
Yi-Lin Yan ◽  
John H. Postlethwait ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Floor Plate ◽  
Slow Muscle ◽  
Pituitary Cells ◽  
Shh Signaling ◽  
Ventral Neural Tube ◽  
Hypothalamic Cells

Sonic hedgehog (Shh) signaling patterns many vertebrate tissues. shh mutations dramatically affect mouse ventral forebrain and floor plate but produce minor defects in zebrafish. Zebrafish have two mammalian Shh orthologs, sonic hedgehog and tiggy-winkle hedgehog, and another gene, echidna hedgehog, that could have overlapping functions. To examine the role of Hedgehog signaling in zebrafish, we have characterized slow muscle omitted (smu) mutants. We show that smu encodes a zebrafish ortholog of Smoothened that transduces Hedgehog signals. Zebrafish smoothened is expressed maternally and zygotically and supports specification of motoneurons, pituitary cells and ventral forebrain. We propose that smoothened is required for induction of lateral floor plate and a subpopulation of hypothalamic cells and for maintenance of medial floor plate and hypothalamic cells.

scholarly journals Ciliary phosphatidylinositol phosphatase Inpp5e plays positive and negative regulatory roles in Shh signaling

2019 ◽  
Author(s):  
Sandii Constable ◽  
Alyssa B. Long ◽  
Katharine A. Floyd ◽  
Stéphane Schurmans ◽  
Tamara Caspary
Keyword(s):  
Signal Transduction ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Relative Timing ◽  
Neural Patterning ◽  
Cell Fates ◽  
Shh Signaling ◽  
Mouse Mutants ◽  
Summary Statement ◽  
Time Required

AbstractSonic hedgehog (Shh) signal transduction specifies ventral cell fates in the neural tube and is mediated by the Gli transcription factors that play both activator (GliA) and repressor (GliR) roles. Cilia are essential for Shh signal transduction and the ciliary phosphatidylinositol phosphatase, Inpp5e, is linked to Shh regulation. In the course of a forward genetic screen for recessive mouse mutants, we identified a functional null allele of Inpp5e, ridge top (rdg), with expanded ventral neural cell fates at E10.5. By E12.5, Inpp5erdg/rdg embryos displayed normal neural patterning and this correction over time required Gli3, the predominant repressor in neural patterning. Inpp5erdg function largely depended on the presence of cilia and on Smoothened, the obligate transducer of Shh signaling, indicating Inpp5e functions within the cilium to regulate the pathway. These data indicate that Inpp5e plays a more complicated role in Shh signaling than previously appreciated. We propose that Inpp5e attenuates Shh signaling in the neural tube through regulation of the relative timing of GliA and GliR production, which is important in understanding how duration of Shh signaling regulates neural tube patterning.Summary statementInpp5e attenuates Sonic hedgehog signal transduction through a combination of positive and negative regulatory roles that likely control the relative timing of Gli processing.

Myogenesis in paraxial mesoderm: preferential induction by dorsal neural tube and by cells expressing Wnt-1

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3675-3686 ◽  
Author(s):  
H.M. Stern ◽  
A.M. Brown ◽  
S.D. Hauschka
Keyword(s):  
Neural Tube ◽  
Muscle Development ◽  
Paraxial Mesoderm ◽  
Myogenic Response ◽  
Dorsal Neural Tube ◽  
Ventral Neural Tube ◽  
Myogenic Induction ◽  
Inductive Activity

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.

Cell-autonomous shift from axial to paraxial mesodermal development in zebrafish floating head mutants

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4257-4264 ◽  
Author(s):  
M.E. Halpern ◽  
C. Thisse ◽  
R.K. Ho ◽  
B. Thisse ◽  
B. Riggleman ◽  
...  
Keyword(s):  
Neural Tube ◽  
Single Cells ◽  
Floor Plate ◽  
Paraxial Mesoderm ◽  
Wild Type ◽  
Genetic Mosaics ◽  
Essential Step ◽  
Ventral Neural Tube ◽  
Mesodermal Development

Zebrafish floating head mutant embryos lack notochord and develop somitic muscle in its place. This may result from incorrect specification of the notochord domain at gastrulation, or from respecification of notochord progenitors to form muscle. In genetic mosaics, floating head acts cell autonomously. Transplanted wild-type cells differentiate into notochord in mutant hosts; however, cells from floating head mutant donors produce muscle rather than notochord in wild-type hosts. Consistent with respecification, markers of axial mesoderm are initially expressed in floating head mutant gastrulas, but expression does not persist. Axial cells also inappropriately express markers of paraxial mesoderm. Thus, single cells in the mutant midline transiently co-express genes that are normally specific to either axial or paraxial mesoderm. Since floating head mutants produce some floor plate in the ventral neural tube, midline mesoderm may also retain early signaling capabilities. Our results suggest that wild-type floating head provides an essential step in maintaining, rather than initiating, development of notochord-forming axial mesoderm.

scholarly journals Sulf1 influences the Shh morphogen gradient during the dorsal ventral patterning of the neural tube in Xenopus tropicalis

2014 ◽  
Vol 391 (2) ◽  
pp. 207-218 ◽  
Author(s):  
Simon A. Ramsbottom ◽  
Richard J. Maguire ◽  
Simon W. Fellgett ◽  
Mary Elizabeth Pownall
Keyword(s):  
Neural Tube ◽  
Xenopus Tropicalis ◽  
Morphogen Gradient

The zebrafish T-box genesno tailandspadetailare required for development of trunk and tail mesoderm and medial floor plate

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3311-3323 ◽  
Author(s):  
Sharon L. Amacher ◽  
Bruce W. Draper ◽  
Brian R. Summers ◽  
Charles B. Kimmel
Keyword(s):  
Embryonic Development ◽  
Neural Tube ◽  
Transcriptional Regulators ◽  
Floor Plate ◽  
Wild Type ◽  
T Box ◽  
No Tail ◽  
Ventral Neural Tube ◽  
Plate Formation ◽  
In Cells

T-box genes encode transcriptional regulators that control many aspects of embryonic development. Here, we demonstrate that the mesodermally expressed zebrafish spadetail (spt)/VegT and no tail (ntl)/Brachyury T-box genes are semi-redundantly and cell-autonomously required for formation of all trunk and tail mesoderm. Despite the lack of posterior mesoderm in spt–;ntl– embryos, dorsal-ventral neural tube patterning is relatively normal, with the notable exception that posterior medial floor plate is completely absent. This contrasts sharply with observations in single mutants, as mutations singly in ntl or spt enhance posterior medial floor plate development. We find that ntl function is required to repress medial floor plate and promote notochord fate in cells of the wild-type notochord domain and that spt and ntl together are required non cell-autonomously for medial floor plate formation, suggesting that an inducing signal present in wild-type mesoderm is lacking in spt–;ntl– embryos.

Direct action of the nodal-related signal cyclops in induction of sonic hedgehog in the ventral midline of the CNS

Development ◽  
2000 ◽  
Vol 127 (18) ◽  
pp. 3889-3897 ◽  
Author(s):  
F. Muller ◽  
S. Albert ◽  
P. Blader ◽  
N. Fischer ◽  
M. Hallonet ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Direct Action ◽  
Brain Regions ◽  
Floor Plate ◽  
Ventral Midline ◽  
Signal Transducers ◽  
Step Model ◽  
Ventral Neural Tube ◽  
Differential Responsiveness

The secreted molecule Sonic hedgehog (Shh) is crucial for floor plate and ventral brain development in amniote embryos. In zebrafish, mutations in cyclops (cyc), a gene that encodes a distinct signal related to the TGF(beta) family member Nodal, result in neural tube defects similar to those of shh null mice. cyc mutant embryos display cyclopia and lack floor plate and ventral brain regions, suggesting a role for Cyc in specification of these structures. cyc mutants express shh in the notochord but lack expression of shh in the ventral brain. Here we show that Cyc signalling can act directly on shh expression in neural tissue. Modulation of the Cyc signalling pathway by constitutive activation or inhibition of Smad2 leads to altered shh expression in zebrafish embryos. Ectopic activation of the shh promoter occurs in response to expression of Cyc signal transducers in the chick neural tube. Furthermore an enhancer of the shh gene, which controls ventral neural tube expression, is responsive to Cyc signal transducers. Our data imply that the Nodal related signal Cyc induces shh expression in the ventral neural tube. Based on the differential responsiveness of shh and other neural tube specific genes to Hedgehog and Cyc signalling, a two-step model for the establishment of the ventral midline of the CNS is proposed.

scholarly journals Neurogenin 1 (Neurog1) expression in the ventral neural tube is mediated by a distinct enhancer and preferentially marks ventral interneuron lineages

2010 ◽  
Vol 340 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Herson I. Quiñones ◽  
Trisha K. Savage ◽  
James Battiste ◽  
Jane E. Johnson
Keyword(s):  
Neural Tube ◽  
Ventral Neural Tube
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