scholarly journals Author response: Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure

2020 ◽  
Author(s):  
Eric R Brooks ◽  
Mohammed Tarek Islam ◽  
Kathryn V Anderson ◽  
Jennifer A Zallen
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Neural Tube Closure ◽  
Author Response ◽  
Sonic Hedgehog Signaling ◽  
Cell Remodeling ◽  
Tube Closure

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.

Sonic hedgehog and the molecular regulation of mouse neural tube closure

Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2507-2517 ◽  
Author(s):  
Patricia Ybot-Gonzalez ◽  
Patricia Cogram ◽  
Dianne Gerrelli ◽  
Andrew J. Copp
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Neural Plate ◽  
Neural Tube Closure ◽  
Molecular Regulation ◽  
Sonic Hedgehog Signaling ◽  
Surface Ectoderm ◽  
Necessary And Sufficient ◽  
Tube Closure

Neural tube closure is a fundamental embryonic event whose molecular regulation is poorly understood. As mouse neurulation progresses along the spinal axis, there is a shift from midline neural plate bending to dorsolateral bending. Here, we show that midline bending is not essential for spinal closure since, in its absence, the neural tube can close by a ‘default’ mechanism involving dorsolateral bending, even at upper spinal levels. Midline and dorsolateral bending are regulated by mutually antagonistic signals from the notochord and surface ectoderm. Notochordal signaling induces midline bending and simultaneously inhibits dorsolateral bending. Sonic hedgehog is both necessary and sufficient to inhibit dorsolateral bending, but is neither necessary nor sufficient to induce midline bending, which seems likely to be regulated by another notochordal factor. Attachment of surface ectoderm cells to the neural plate is required for dorsolateral bending, which ensures neural tube closure in the absence of sonic hedgehog signaling.

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

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Eric R Brooks ◽  
Mohammed Tarek 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

Neural 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 flat 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.

scholarly journals Author response: ARL13B regulates Sonic hedgehog signaling from outside primary cilia

2019 ◽  
Author(s):  
Eduardo D Gigante ◽  
Megan R Taylor ◽  
Anna A Ivanova ◽  
Richard A Kahn ◽  
Tamara Caspary
Keyword(s):  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Author Response ◽  
Sonic Hedgehog Signaling

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.

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.

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