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Updated: May 7, 2026

The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions
Published on: February 16, 2017
Multiple signaling pathways coordinate to induce a threshold response in a chordate embryo
1Department of Zoology, Graduate School of Science, Kyoto University, Sakyo, Kyoto, Japan.
Abstract:
In animal development, secreted signaling molecules evoke all-or-none threshold responses of target gene transcription to specify cell fates. In the chordate Ciona intestinalis, the neural markers Otx and Nodal are induced at early embryonic stages by Fgf9/16/20 signaling. Here we show that three additional signaling molecules act negatively to generate a sharp expression boundary for neural genes. EphrinA signaling antagonizes FGF signaling by inhibiting ERK phosphorylation more strongly in epidermal cells than in neural cells, which accentuates differences in the strength of ERK activation. However, even weakly activated ERK activates Otx and Nodal transcription occasionally, probably because of the inherently stochastic nature of signal transduction processes and binding of transcription factors to target sequences. This occasional and undesirable activation of neural genes by weak residual ERK activity is directly repressed by Smad transcription factors activated by Admp and Gdf1/3-like signaling, further sharpening the differential responses of cells to FGF signaling. Thus, these signaling pathways coordinate to evoke a threshold response that delineates a sharp expression boundary.
Insights
Secreted signaling molecules control cell fate by triggering threshold responses in gene transcription. In Ciona intestinalis, EphrinA and Smad pathways refine neural gene boundaries by antagonizing FGF signaling, ensuring precise cell differentiation.
Area of Science:
- Developmental biology
- Cell signaling
- Molecular genetics
Background:
- Secreted signaling molecules induce threshold responses for cell fate specification in animal development.
- Fibroblast Growth Factor (FGF) signaling initiates neural gene expression (Otx, Nodal) in early Ciona intestinalis embryos.
Purpose of the Study:
- To investigate the role of additional signaling molecules in sharpening neural gene expression boundaries.
- To elucidate the mechanisms by which EphrinA and Smad pathways refine FGF-induced neural gene expression.
Main Methods:
- Analysis of gene expression patterns in Ciona intestinalis embryos.
- Investigating the interplay between FGF, EphrinA, and Smad signaling pathways.
- Examining the regulation of ERK phosphorylation and transcription factor activity.
Main Results:
- EphrinA signaling antagonizes FGF signaling by differentially inhibiting ERK phosphorylation in neural versus epidermal cells.
- Smad transcription factors, activated by Admp and Gdf1/3-like signaling, repress occasional neural gene activation by residual ERK activity.
- These coordinated signaling events establish a sharp expression boundary for neural genes.
Conclusions:
- A network of signaling pathways, including FGF, EphrinA, and Smad, precisely controls cell fate determination.
- The interplay between these pathways generates a robust threshold response, delineating sharp boundaries for neural gene expression.
- This mechanism ensures accurate cell fate specification during embryonic development.
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