scholarly journals Region-specific requirement for cholesterol modification of sonic hedgehog in patterning the telencephalon and spinal cord

Development ◽  
2007 ◽  
Vol 134 (11) ◽  
pp. 2095-2105 ◽  
Author(s):  
X. Huang ◽  
Y. Litingtung ◽  
C. Chiang
Keyword(s):  
Spinal Cord ◽  
Sonic Hedgehog ◽  
Specific Requirement ◽  
Cholesterol Modification

scholarly journals Sonic Hedgehog modulates the inflammatory response and improves functional recovery after spinal cord injury in a thoracic contusion–compression model

2021 ◽  
Author(s):  
Hao Zhang ◽  
Alexander Younsi ◽  
Guoli Zheng ◽  
Mohamed Tail ◽  
Anna-Kathrin Harms ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Sonic Hedgehog ◽  
Functional Recovery ◽  
Intrathecal Administration ◽  
Neuroprotective Effects ◽  
Thoracic Spinal Cord ◽  
Shh Pathway ◽  
Thoracic Spinal ◽  
Cord Injury

Abstract Purpose The Sonic Hedgehog (Shh) pathway has been associated with a protective role after injury to the central nervous system (CNS). We, therefore, investigated the effects of intrathecal Shh-administration in the subacute phase after thoracic spinal cord injury (SCI) on secondary injury processes in rats. Methods Twenty-one Wistar rats were subjected to thoracic clip-contusion/compression SCI at T9. Animals were randomized into three treatment groups (Shh, Vehicle, Sham). Seven days after SCI, osmotic pumps were implanted for seven-day continuous intrathecal administration of Shh. Basso, Beattie and Bresnahan (BBB) score, Gridwalk test and bodyweight were weekly assessed. Animals were sacrificed six weeks after SCI and immunohistological analyses were conducted. The results were compared between groups and statistical analysis was performed (p < 0.05 was considered significant). Results The intrathecal administration of Shh led to significantly increased polarization of macrophages toward the anti-inflammatory M2-phenotype, significantly decreased T-lymphocytic invasion and significantly reduced resident microglia six weeks after the injury. Reactive astrogliosis was also significantly reduced while changes in size of the posttraumatic cyst as well as the overall macrophagic infiltration, although reduced, remained insignificant. Finally, with the administration of Shh, gain of bodyweight (216.6 ± 3.65 g vs. 230.4 ± 5.477 g; p = 0.0111) and BBB score (8.2 ± 0.2 vs. 5.9 ± 0.7 points; p = 0.0365) were significantly improved compared to untreated animals six weeks after SCI as well. Conclusion Intrathecal Shh-administration showed neuroprotective effects with attenuated neuroinflammation, reduced astrogliosis and improved functional recovery six weeks after severe contusion/compression SCI.

Sonic hedgehog-dependent emergence of oligodendrocytes in the telencephalon: evidence for a source of oligodendrocytes in the olfactory bulb that is independent of PDGFRα signaling

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 4993-5004
Author(s):  
Nathalie Spassky ◽  
Katharina Heydon ◽  
Arnaud Mangatal ◽  
Alexandar Jankovski ◽  
Christelle Olivier ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Olfactory Bulb ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Molecular Mechanisms ◽  
Cell Contact ◽  
Sonic Hedgehog Signaling ◽  
Oligodendrocyte Progenitors

Most studies on the origin of oligodendrocyte lineage have been performed in the spinal cord. By contrast, molecular mechanisms that regulate the appearance of the oligodendroglial lineage in the brain have not yet attracted much attention. We provide evidence for three distinct sources of oligodendrocytes in the mouse telencephalon. In addition to two subpallial ventricular foci, the anterior entopeduncular area and the medial ganglionic eminence, the rostral telencephalon also gives rise to oligodendrocytes. We show that oligodendrocytes in the olfactory bulb are generated within the rostral pallium from ventricular progenitors characterized by the expression of Plp. We provide evidence that these Plp oligodendrocyte progenitors do not depend on signal transduction mediated by platelet-derived growth factor receptors (PDGFRs), and therefore propose that they belong to a different lineage than the PDGFRα-expressing progenitors. Moreover, induction of oligodendrocytes in the telencephalon is dependent on sonic hedgehog signaling, as in the spinal cord. In all these telencephalic ventricular territories, oligodendrocyte progenitors were detected at about the same developmental stage as in the spinal cord. However, both in vivo and in vitro, the differentiation into O4-positive pre-oligodendrocytes was postponed by 4-5 days in the telencephalon in comparison with the spinal cord. This delay between determination and differentiation appears to be intrinsic to telencephalic oligodendrocytes, as it was not shortened by diffusible or cell-cell contact factors present in the spinal cord.

scholarly journals Cadherin-7 enhances Sonic Hedgehog signalling by preventing Gli3 repressor formation during neural tube patterning

Open Biology ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. 170225 ◽  
Author(s):  
Rie Kawano ◽  
Kunimasa Ohta ◽  
Giuseppe Lupo
Keyword(s):  
Spinal Cord ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Target Genes ◽  
Dorsoventral Patterning ◽  
Dorsal Spinal Cord ◽  
Suppressor Of Fused ◽  
Intracellular Movement ◽  
Sonic Hedgehog Signalling ◽  
Dorsal Spinal

Sonic Hedgehog (Shh) is a ventrally enriched morphogen controlling dorsoventral patterning of the neural tube. In the dorsal spinal cord, Gli3 protein bound to suppressor-of-fused (Sufu) is converted into Gli3 repressor (Gli3R), which inhibits Shh-target genes. Activation of Shh signalling prevents Gli3R formation, promoting neural tube ventralization. We show that cadherin-7 (Cdh7) expression in the intermediate spinal cord region is required to delimit the boundary between the ventral and the dorsal spinal cord. We demonstrate that Cdh7 functions as a receptor for Shh and enhances Shh signalling. Binding of Shh to Cdh7 promotes its aggregation on the cell membrane and association of Cdh7 with Gli3 and Sufu. These interactions prevent Gli3R formation and cause Gli3 protein degradation. We propose that Shh can act through Cdh7 to limit intracellular movement of Gli3 protein and production of Gli3R, thus eliciting more efficient activation of Gli-dependent signalling.

scholarly journals EPH/EPHRIN SIGNALING CONTROLS PROGENITOR IDENTITIES IN THE VENTRAL SPINAL CORD

2016 ◽  
Author(s):  
Julien Laussu ◽  
Christophe Audouard ◽  
Anthony Kischel ◽  
Poincyane Assis-Nascimento ◽  
Nathalie Escalas ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Sonic Hedgehog ◽  
Cell Communication ◽  
Dependent Manner ◽  
Eph Receptors ◽  
Loss Of Function ◽  
Summary Statement ◽  
Dose Dependent ◽  
Ventral Spinal Cord

SUMMARY STATEMENTThis article by Laussu et al. describes a role for Eph:ephrin signaling in controlling the identity of neural progenitors in the ventral spinal cord.Early specification of progenitors of the ventral spinal cord involves the morphogen Sonic Hedgehog which induces distinct progenitor identities in a dose-dependent manner. Following these initial patterning events, progenitor identities have to be maintained in order to generate appropriate numbers of progeny. Here we provide evidence that communication via Eph:ephrin signaling is required to maintain progenitor identities in the ventral spinal cord. We show that ephrinB2 and ephrinB3 are expressed in restricted progenitor domains in the ventral spinal cord while several Eph receptors are more broadly expressed. Further, we provide evidence that expression of Efnb3 and EphA4 is controlled by Shh. Genetic loss-of-function analyses indicate that expression of ephrinB2 and ephrinB3 is required to control progenitor identities and in vitro experiments reveal that activation of Eph forward signaling in spinal progenitors up-regulates the expression of the identity transcription factor Nkx2.2. Altogether our results indicate that cell-to-cell communication is necessary to control progenitor identity in the ventral spinal cord.

scholarly journals The effect of sonic hedgehog on motor neuron positioning in the spinal cord during chicken embryo development

2017 ◽  
Author(s):  
Ciqing Yang ◽  
Xiaoying Li ◽  
Qiuling Li ◽  
Qiong Li ◽  
Han Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Embryo Development ◽  
Sonic Hedgehog ◽  
Motor Neurons ◽  
Chicken Embryo ◽  
Positional Information ◽  
Underlying Mechanism ◽  
Correct Location ◽  
Information Cell

ABSTRACTSonic hedgehog (Shh) is a vertebrate homologue of the secreted Drosophila protein hedgehog, and is expressed by the notochord and the floor plate in the developing spinal cord. Shh provides signals relevant for positional information, cell proliferation, and possibly cell survival depending on the time and location of the expression. Although the role of Shh in providing positional information in the neural tube has been experimentally proven, the exact underlying mechanism still remains unclear. In this study, we report that overexpression of Shh affects motor neuron positioning in the spinal cord during chicken embryo development by inducing abnormalities in the structure of the motor column and motor neuron integration. In addition, Shh overexpression inhibits the expression of dorsal transcription factors and commissural axon projections. Our results indicate that correct location of Shh expression is the key to the formation of the motor column. In conclusion, the overexpression of Shh in the spinal cord not only affects the positioning of motor neurons, but also induces abnormalities in the structure of the motor column.

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