Abstract
The signal regulated transcription factors (SRTFs) control the ultimate transcriptional output of signaling pathways. Here, we examined a family of FGF-induced SRTFs - Etv1, Etv 4, and Etv 5 - in murine lens development. Contrary to FGF receptor mutants that displayed loss of ERK signaling and defective cell differentiation, Etv deficiency augmented ERK phosphorylation without disrupting the normal lens fiber gene expression. Instead, the transitional zone for lens differentiation was shifted anteriorly as a result of reduced Jag1-Notch signaling. We also showed that Etv proteins suppresses mTOR activity by promoting Tsc2 expression, which is necessary for the nuclei clearance in mature lens. These results revealed the functional divergence between Etv and FGF in lens development, demonstrating that these SRTFs can operate outside the confine of their upstream signaling.
Highlights
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
These results revealed the critical differences between the function of Etv family transcription factors and FGF signaling during lens development, demonstrating that these signal-regulated transcription factor (SRTF) can operate outside the confine of upstream signaling
Previous studies have shown that Etv transcription factors are controlled by FGF signaling during embryonic development
Summary
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. Transgenic overexpression of Fgf or Fgf resulted in premature differentiation of lens epithelial cells (Collins et al, 2018; Robinson et al, 1998; Robinson et al, 1995b), whereas over-activation of FGF signaling as a result of Nf1 and Spry1/2 deletion disrupted lens induction and lens fiber cell differentiation, respectively (Carbe and Zhang, 2011; Kuracha et al, 2011) These results demonstrated that the FGF signaling cascade is critical for lens development, but the direct downstream transcriptional effectors of FGF signaling were not well understood. These results revealed the critical differences between the function of Etv family transcription factors and FGF signaling during lens development, demonstrating that these SRTFs can operate outside the confine of upstream signaling
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