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 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

Angiogenesis within the developing mouse neural tube is dependent on sonic hedgehog signaling: possible roles of motor neurons

2005 ◽  
Vol 10 (6) ◽  
pp. 595-604 ◽  
Author(s):  
Takashi Nagase ◽  
Miki Nagase ◽  
Kotaro Yoshimura ◽  
Toshiro Fujita ◽  
Isao Koshima
Keyword(s):  
Sonic Hedgehog ◽  
Motor Neurons ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Sonic Hedgehog Signaling

Sonic hedgehog synergizes with the extracellular matrix protein vitronectin to induce spinal motor neuron differentiation

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 333-342 ◽  
Author(s):  
S. Pons ◽  
E. Marti
Keyword(s):  
Extracellular Matrix ◽  
Motor Neuron ◽  
Sonic Hedgehog ◽  
Motor Neurons ◽  
Neural Tube ◽  
Matrix Protein ◽  
Floor Plate ◽  
Binding Domain ◽  
Extracellular Matrix Protein ◽  
Neuron Differentiation

Patterning of the vertebrate neural tube depends on intercellular signals emanating from sources such as the notochord and the floor plate. The secreted protein Sonic hedgehog and the extracellular matrix protein Vitronectin are both expressed in these signalling centres and have both been implicated in the generation of ventral neurons. The proteolytic processing of Sonic hedgehog is fundamental for its signalling properties. This processing generates two secreted peptides with all the inducing activity of Shh residing in the highly conserved 19 kDa amino-terminal peptide (N-Shh). Here we show that Vitronectin is also proteolitically processed in the embryonic chick notochord, floor plate and ventral neural tube and that this processing is spatiotemporally correlated with the generation of motor neurons. The processing of Vitronectin produces two fragments of 54 kDa and 45 kDa, as previously described for Vitronectin isolated from chick yolk. The 45 kDa fragment lacks the heparin-binding domain and the integrin-binding domain, RGD, present in the non-processed Vitronectin glycoprotein. Here we show that N-Shh binds to the three forms of Vitronectin (70, 54 and 45 kDa) isolated from embryonic tissue, although is preferentially associated with the 45 kDa form. Furthermore, in cultures of dissociated neuroepithelial cells, the combined addition of N-Shh and Vitronectin significantly increases the extent of motor neuron differentiation, as compared to the low or absent inducing capabilities of either N-Shh or Vitronectin alone. Thus, we conclude that the differentiation of motor neurons is enhanced by the synergistic action of N-Shh and Vitronectin, and that Vitronectin may be necessary for the proper presentation of the morphogen N-Shh to one of its target cells, the differentiating motor neurons.

Sonic hedgehog signaling at gastrula stages specifies ventral telencephalic cells in the chick embryo

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3283-3293 ◽  
Author(s):  
L. Gunhaga ◽  
T.M. Jessell ◽  
T. Edlund
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Early Stage ◽  
Primitive Streak ◽  
Cell Types ◽  
Neural Cells ◽  
Sonic Hedgehog Signaling ◽  
Ventral Telencephalon ◽  
Prechordal Mesoderm

A secreted signaling factor, Sonic hedgehog (Shh), has a crucial role in the generation of ventral cell types along the entire rostrocaudal axis of the neural tube. At caudal levels of the neuraxis, Shh is secreted by the notochord and floor plate during the period that ventral cell fates are specified. At anterior prosencephalic levels that give rise to the telencephalon, however, neither the prechordal mesoderm nor the ventral neural tube expresses Shh at the time that the overt ventral character of the telencephalon becomes evident. Thus, the precise role and timing of Shh signaling relevant to the specification of ventral telencephalic identity remains unclear. By analysing neural cell differentiation in chick neural plate explants we provide evidence that neural cells acquire molecular properties characteristic of the ventral telencephalon in response to Shh signals derived from the anterior primitive streak/Hensen's node region at gastrula stages. Exposure of prospective anterior prosencephalic cells to Shh at this early stage is sufficient to initiate a temporal program of differentiation that parallels that of neurons generated normally in the medial ganglionic eminence subdivision of the ventral telencephalon.

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 Gene Regulatory Logic for Reading the Sonic Hedgehog Signaling Gradient in the Vertebrate Neural Tube

Cell ◽  
2012 ◽  
Vol 148 (1-2) ◽  
pp. 273-284 ◽  
Author(s):  
Nikolaos Balaskas ◽  
Ana Ribeiro ◽  
Jasmina Panovska ◽  
Eric Dessaud ◽  
Noriaki Sasai ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Sonic Hedgehog Signaling ◽  
Gene Regulatory
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