Name
Title | ||
|---|---|---|
Neural fate decisions mediated by trans-activation and cis-inhibition in Notch signaling. |
Abstract | ||
|---|---|---|
In the developing nervous system, the expression of proneural genes, i.e. Hes1, Neurogenin-2 (Ngn2) and Deltalike-1 (Dll1), oscillates in neural progenitors with a period of 2-3 h, but is persistent in post-mitotic neurons. Unlike the synchronization of segmentation clocks, oscillations in neural progenitors are asynchronous between cells. It is known that Notch signaling, in which Notch in a cell can be activated by Dll1 in neighboring cells (trans-activation) and can also be inhibited by Dll1 within the same cell (cis-inhibition), is important for neural fate decisions. There have been extensive studies of trans-activation, but the operating mechanisms and potential implications of cis-inhibition are less clear and need to be further investigated.In this article, we present a computational model for neural fate decisions based on intertwined dynamics with trans-activation and cis-inhibition involving the Hes1, Notch and Dll1 proteins. In agreement with experimental observations, the model predicts that both trans-activation and cis-inhibition play critical roles in regulating the choice between remaining as a progenitor and embarking on neural differentiation. In particular, trans-activation is essential for generation of oscillations in neural progenitors, and cis-inhibition is important for the asynchrony between adjacent cells, indicating that the asynchronous oscillations in neural progenitors depend on cooperation between trans-activation and cis-inhibition. In contrast, cis-inhibition plays more critical roles in embarking on neural differentiation by inactivating intercellular Notch signaling. The model presented here might be a good candidate for providing the first qualitative mechanism of neural fate decisions mediated by both trans-activation and cis-inhibition. |
Year | DOI | Venue |
|---|---|---|
2011 | 10.1093/bioinformatics/btr551 | Bioinformatics |
Keywords | Field | DocType |
neighboring cell,neural progenitor,critical role,asynchronous oscillation,adjacent cell,neural differentiation,dll1 protein,computational model,neural fate decision,intercellular notch | Anatomy,Neuroscience,Asynchrony,Progenitor,Biology,Cell,Proneural genes,Nervous system,Bioinformatics,Notch signaling pathway,HES1,Progenitor cell | Journal |
Volume | Issue | ISSN |
27 | 22 | 1367-4811 |
Citations | PageRank | References |
2 | 0.68 | 1 |
Authors | ||
4 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Ruiqi Wang | 1 | 64 | 15.44 |
| Kaihui Liu | 2 | 2 | 0.68 |
| Luonan Chen | 3 | 1485 | 145.71 |
| Kazuyuki Aihara | 4 | 1909 | 333.03 |