Etv transcription factors functionally diverge from their upstream FGF signaling in lens development

The signal regulated transcription factors (SRTFs) control the ultimate transcriptional output of signaling pathways.

these SRTFs can operate outside the confine of their upstream signaling.

Many cells contain proteins known as signal-induced transcription factors, which are poised to receive messages from the environment and then react by activating genes required for the cell to respond appropriately.

It is commonly thought that these transcription factors faithfully follow the instructions they receive from the external signal: for instance, if the message was to encourage the cell to grow, the transcription factors would switch on growth-related genes.

Transcription factors control the ultimate fate of a cell, and there is therefore increased interest in targeting them for therapy. The work by Garg, Hannan, Wang et al. reveals an unexpected complexity in how these proteins respond to upstream signals, highlighting the importance of further dissecting these relationships.

The cell signaling networks are commonly depicted in a hierarchical manner, starting with the binding of extracellular ligands to cell surface receptors, followed by the relay of cytoplasmic mediators, and culminating in the activation of nuclear transcription factors. In this unidirectional view, each signal-regulated transcription factor (SRTF) is expected to control a subset of the transcriptional output of upstream signaling

This model has been confirmed in many systems. For example, the transcriptomic changes induced by BMP, Hedgehog and Wnt signaling can be readily accounted for by their transcription effectors Smad, Gli and β-catenin, respectively. However, whether this principle applies to the SRTFs for FGF signaling remains to be determined.

SRTFs constitute a special class of transcription factors that relay intracellular signals to shape the cellular transcriptome, which ultimately determines the identity and status of the cell.

our current study paints a more complex picture of Etv activity, suggesting that their functions deviate considerably from their upstream FGF signaling. As transcription factors attract increasing interests as viable therapeutic targets, it will be important to elucidate the context-dependent function of these SRTFs in development and diseases.