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E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3

D Chen1, Y Chen, D Forrest

  • 1Department of Ophthalmology and Visual Science, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Cell Death and Differentiation
|April 6, 2013
PubMed

Insights

Activating transcription factors E2F1-3 drive cell division. In vivo studies reveal E2F2, not just E2F1, can induce apoptosis in retinal cone photoreceptors through distinct pathways.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Neuroscience

Background:

  • Activating E2F transcription factors (E2F1-3) are known to induce cell division.
  • Previous studies suggested E2F1 is the primary driver of apoptosis, with other E2Fs acting indirectly.
  • Retinal development provides a model to study in vivo E2F functions beyond cell division.

Purpose of the Study:

  • To investigate the in vivo functions of adenovirus E2 promoter binding factor (E2f) family members in the developing retina.
  • To elucidate the distinct roles of E2F1 and E2F2 in apoptosis of retinal neurons, particularly cone photoreceptors.

Main Methods:

  • Analysis of mouse models with genetic alterations in retinoblastoma (Rb) and its relative p107.
  • In vivo assessment of apoptosis in different retinal neuron types (rod, bipolar, ganglion, and cone photoreceptors).
  • Examination of the involvement of E2F1, E2F2, E2F3, p53, and p73 in these apoptotic pathways.

Main Results:

  • Retinal neurons lacking Rb and p107 undergo apoptosis.
  • E2F1 induces apoptosis in rod, bipolar, and ganglion neurons, but not cone photoreceptors.
  • E2F2 is essential and sufficient for cone photoreceptor apoptosis, independent of E2F1 and E2F3, and involves p53.
  • E2F1-dependent apoptosis occurs independently of p53 and p73.

Conclusions:

  • E2F-induced apoptosis can occur independently of E2F1, with E2F2 playing a critical role in cone photoreceptor death.
  • Distinct apoptotic pathways are activated by E2F1 and E2F2 in response to tumorigenic insults in the retina.
  • This study provides in vivo evidence for context-specific functions of E2F family members in cell death.

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