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
•Dissertation
Investigating gene regulatory networks underlying zebrafish pigment cell development
Kleio Petratou
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TL;DR: The core GRN guiding specification of the NC-derived iridophore lineage is established using systems biology and results reveal previously unacknowledged molecular mechanisms underlying fate choice and demonstrate the value of integrating experimental and mathematical approaches when investigating GRNs.
Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics
Andreas Sagner,Zachary B. Gaber,Julien Delile,Jennifer H. Kong,David Rousso,Caroline A. Pearson,Steven E. Weicksel,S. Neda Mousavy Gharavy,James Briscoe,Bennett G. Novitch +9 more
TL;DR: A tight coupling between the regulatory networks that control patterning and neuronal differentiation is revealed, and how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation is demonstrated.
Neural tube development depends on notochord-derived Sonic hedgehog released into the sclerotome
Nitza Kahane,Chaya Kalcheim +1 more
TL;DR: The results reveal that the sclerotome is a potential site of a Shh gradient that coordinates development of mesodermal and neural progenitors and is also necessary for neural tube development.
Cytoneme signaling provides essential contributions to mammalian tissue patterning
Eric T. Hall,Miriam E. Dillard,Elizabeth R. Cleverdon,Yan Zhang,Christina A. Daly,Shariq S. Ansari,Randall Wakefield,Daniel P. Stewart,Shondra M. Pruett-Miller,Alfonso Lavado,Alex F. Carisey,Amanda Johnson,Yong-Dong Wang,Emma Selner,M. Tanes,Young Sang Ryu,Camenzind G. Robinson,Jeffrey Steinberg,Stacey K. Ogden +18 more
TL;DR: A mouse model for compromised sonic hedgehog (SHH) morphogen delivery is developed and it is discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes, suggesting MYO10 is a key regulator of cytoneme function.
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