Signaling by the TGF-beta homolog decapentaplegic functions reiteratively within the network of genes controlling retinal cell fate determination in Drosophila

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 935-943 ◽  
Author(s):  
R. Chen ◽  
G. Halder ◽  
Z. Zhang ◽  
G. Mardon
Keyword(s):  
Cell Fate ◽  
Retinal Cell ◽  
Cell Fate Determination ◽  
Tgf Beta ◽  
Eyes Absent ◽  
Fate Determination ◽  
Sine Oculis ◽  
Retinal Determination ◽  
Interactive Network ◽  
Distinct Cell

Retinal cell fate determination in Drosophila is controlled by an interactive network of genes, including eyeless, eyes absent, sine oculis and dachshund. We have investigated the role of the TGF-beta homolog decapentaplegic in this pathway. We demonstrate that, during eye development, while eyeless transcription does not depend on decapentaplegic activity, the expression of eyes absent, sine oculis and dachshund are greatly reduced in a decapentaplegic mutant background. We also show that decapentaplegic signaling acts synergistically with and at multiple levels of the retinal determination network to induce eyes absent, sine oculis and dachshund expression and ectopic eye formation. These results suggest a mechanism by which a general patterning signal such as Decapentaplegic cooperates reiteratively with tissue-specific factors to determine distinct cell fates during development.

scholarly journals Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Fuqing Wu ◽  
Ri-Qi Su ◽  
Ying-Cheng Lai ◽  
Xiao Wang
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Cell Fate Determination ◽  
Final States ◽  
Cell Fates ◽  
Fate Determination ◽  
Cellular Decision Making ◽  
Distinct Cell ◽  
Model Predictions ◽  
Gene Regulatory

The process of cell fate determination has been depicted intuitively as cells travelling and resting on a rugged landscape, which has been probed by various theoretical studies. However, few studies have experimentally demonstrated how underlying gene regulatory networks shape the landscape and hence orchestrate cellular decision-making in the presence of both signal and noise. Here we tested different topologies and verified a synthetic gene circuit with mutual inhibition and auto-activations to be quadrastable, which enables direct study of quadruple cell fate determination on an engineered landscape. We show that cells indeed gravitate towards local minima and signal inductions dictate cell fates through modulating the shape of the multistable landscape. Experiments, guided by model predictions, reveal that sequential inductions generate distinct cell fates by changing landscape in sequence and hence navigating cells to different final states. This work provides a synthetic biology framework to approach cell fate determination and suggests a landscape-based explanation of fixed induction sequences for targeted differentiation.

Sign in / Sign up

Export Citation Format

Share Document