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.

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 Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure

2020 ◽  
Author(s):  
Eric R. Brooks ◽  
Mohammed T. Islam ◽  
Kathryn V. Anderson ◽  
Jennifer A. Zallen
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Structural Changes ◽  
Neural Tube Closure ◽  
Mammalian Brain ◽  
Shh Signaling ◽  
Apical Constriction ◽  
Cell Remodeling ◽  
Tube Closure

AbstractNeural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are short with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constriction, driving neural fold elevation. Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architecture, whereas embryos with expanded Shh signaling, including the IFT-A complex mutants Ift122 and Ttc21b and embryos expressing activated Smoothened, display apical constriction defects in lateral cells. Disruption of lateral, but not midline, cell remodeling results in exencephaly. These results reveal a morphogenetic program of patterned apical constriction governed by Shh signaling that generates structural changes in the developing mammalian brain.

FoxF1 is Required for Ciliogenesis and Distribution of Sonic Hedgehog Signaling Components in Cilium

2019 ◽  
Vol 19 (5) ◽  
pp. 326-334
Author(s):  
Lu Huang ◽  
Marco Tjakra ◽  
Desha Luo ◽  
Lin Wen ◽  
Daoxi Lei ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
3T3 Cells ◽  
Shh Signaling ◽  
Nih 3T3 ◽  
Signaling Components ◽  
Nih 3T3 Cells

Background: In vertebrates, cilium is crucial for Hedgehog signaling transduction. Forkhead box transcriptional factor FoxF1 is reported to be associated with Sonic Hedgehog (Shh) signaling in many cases. However, the role of FoxF1 in cilium remains unknown. Here, we showed an essential role of FoxF1 in the regulation of ciliogenesis and in the distribution of Shh signaling components in cilium. Methods: NIH/3T3 cells were serum starved for 24h to induce cilium. Meanwhile, shRNA was used to knockdown the FoxF1 expression in the cells and CRISPR/Cas9 was used to generate the FoxF1 zebrafish mutant. The mRNA and protein expression of indicated genes were detected by the qRT-PCR and western blot, respectively. Immunofluorescence staining was performed to detect the cilium and Shh components distribution. Results: FoxF1 knockdown decreased the cilium length in NIH/3T3 cells. Meanwhile, the disruption of FoxF1 function inhibited the expression of cilium-related genes and caused an abnormal distribution of Shh components in the cilium. Furthermore, homozygous FoxF1 mutants exhibited defective development of pronephric cilium in early zebrafish embryos. Conclusion: Together, our data illustrated that FoxF1 is required for ciliogenesis in vitro and in vivo and for the proper localization of Shh signaling components in cilium.

Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2533-2543 ◽  
Author(s):  
Q. Ding ◽  
J. Motoyama ◽  
S. Gasca ◽  
R. Mo ◽  
H. Sasaki ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Motor Neurons ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Zinc Finger Protein ◽  
Floor Plate ◽  
Mutant Mice ◽  
Sonic Hedgehog Signaling ◽  
Cubitus Interruptus ◽  
High Level

Floor plate cells at the midline of the neural tube are specified by high-level activity of Sonic hedgehog (Shh) secreted by notochord, whereas motor neurons are thought to be specified by a lower level activity of Shh secreted in turn by floor plate cells. In Drosophila, the Gli zinc finger protein Cubitus interruptus functions as a transcription factor activating Hedgehog-responsive genes. We report that the expression of known Shh-responsive genes such as Ptc and Gli1 is downregulated in mutant mice lacking Gli2 function. Gli2 mutants fail to develop a floor plate yet still develop motor neurons, which occupy the ventral midline of the neural tube. Our results imply that Gli2 is required to mediate high level but not low level Shh activity and show that the development of motor neurons can occur in the absence of floor plate induction.

scholarly journals Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea

2015 ◽  
Vol 112 (12) ◽  
pp. 3746-3751 ◽  
Author(s):  
Eun Jin Son ◽  
Ji-Hyun Ma ◽  
Harinarayana Ankamreddy ◽  
Jeong-Oh Shin ◽  
Jae Young Choi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sonic Hedgehog ◽  
Hair Cells ◽  
Floor Plate ◽  
Basilar Papilla ◽  
Apical Region ◽  
Shh Signaling ◽  
Sensory Hair ◽  
Sensory Hair Cells

Sound frequency discrimination begins at the organ of Corti in mammals and the basilar papilla in birds. Both of these hearing organs are tonotopically organized such that sensory hair cells at the basal (proximal) end respond to high frequency sound, whereas their counterparts at the apex (distal) respond to low frequencies. Sonic hedgehog (Shh) secreted by the developing notochord and floor plate is required for cochlear formation in both species. In mice, the apical region of the developing cochlea, closer to the ventral midline source of Shh, requires higher levels of Shh signaling than the basal cochlea farther away from the midline. Here, gain-of-function experiments using Shh-soaked beads in ovo or a mouse model expressing constitutively activated Smoothened (transducer of Shh signaling) show up-regulation of apical genes in the basal cochlea, even though these regionally expressed genes are not necessarily conserved between the two species. In chicken, these altered gene expression patterns precede morphological and physiological changes in sensory hair cells that are typically associated with tonotopy such as the total number of stereocilia per hair cell and gene expression of an inward rectifier potassium channel, IRK1, which is a bona fide feature of apical hair cells in the basilar papilla. Furthermore, our results suggest that this conserved role of Shh in establishing cochlear tonotopy is initiated early in development by Shh emanating from the notochord and floor plate.

scholarly journals Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube

2010 ◽  
Vol 24 (11) ◽  
pp. 1186-1200 ◽  
Author(s):  
V. Ribes ◽  
N. Balaskas ◽  
N. Sasai ◽  
C. Cruz ◽  
E. Dessaud ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Floor Plate ◽  
Sonic Hedgehog Signaling ◽  
Neuronal Progenitors ◽  
Signaling Dynamics

scholarly journals 13-P065 How long does ventral neural tube patterning need Sonic Hedgehog signaling?

2009 ◽  
Vol 126 ◽  
pp. S214
Author(s):  
Noriaki Sasai ◽  
Eric Dessaud ◽  
Vanessa Ribes ◽  
James Briscoe
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Sonic Hedgehog Signaling ◽  
Ventral Neural Tube
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