Establishing and Interpreting Graded Sonic Hedgehog Signaling during Vertebrate Neural Tube Patterning: The Role of Negative Feedback
Vanessa Ribes,James Briscoe +1 more
TL;DR: Together, these mechanisms exemplify a strategy for morphogen interpretation, which is termed temporal adaptation that relies on the continuous processing and refinement of the cellular response to the graded signal.
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Abstract: The secreted protein Sonic Hedgehog (SHH) acts in graded fashion to pattern the dorsal-ventral axis of the vertebrate neural tube. This is a dynamic process in which increasing concentrations and durations of exposure to SHH generate neurons with successively more ventral identities. Interactions between the receiving cells and the graded signal underpin the mechanism of SHH action. In particular, negative feedback, involving proteins transcriptionally induced or repressed by SHH signaling, plays an essential role in shaping the graded readout. On one hand, negative feedback controls, in a noncell-autonomous manner, the distribution of SHH across the field of receiving cells. On the other, it acts cell-autonomously to convert different concentrations of SHH into distinct durations of intracellular signal transduction. Together, these mechanisms exemplify a strategy for morphogen interpretation, which we have termed temporal adaptation that relies on the continuous processing and refinement of the cellular response to the graded signal.
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Citations
Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord
Cathy Danesin,Romain Darche-Gabinaud,Nathalie Escalas,Vanessa Bouguetoch,Philippe Cochard,Amir Al Oustah,David Ohayon,Bruno Glise,Cathy Soula +8 more
TL;DR: In this article, the authors defined Sulf2a as a player in the control of Sonic Hedgehog (Shh)-mediated cell type specification during spinal cord development and showed that Sulf 2a depletion in zebrafish results in overproduction of V3 interneurons at the expense of motor neurons and also impedes generation of oligodendrocyte precursor cells.
Dissecting Signaling Pathways that Regulate Axonal Guidance Effects of Sonic Hedgehog: A Dissertation
Daorong Guo
- 01 Jan 2011
TL;DR: It is shown that high concentrations of Shh induce growth cone collapse and repulsive turning of the chick RGC through rapid increase of Ca in the growth cone, and specific activation of PKCα and Rho signaling pathways, and that integrin linked kinase (ILK) acts as an immediate downstream effector ofPKCα.
Transient primary cilia mediate robust Hedgehog pathway-dependent cell cycle control
TL;DR: It is proposed that the ability of cells to integrate Hh pathway activity from more than one cell cycle imparts robustness on Hh pathways control of proliferation and may have implications for other Hh-mediated events in development.
Anti-epileptic drugs and brain and behavioural development in animal models and humans
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TL;DR: A simple but extensive computational model is presented that considers the detailed reaction mechanisms involved in the hedgehog signal transduction and provides a detailed insight into regulation of GLI.
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