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Related Experiment Videos

A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting

G J Lindeman1, L Dagnino, S Gaubatz

  • 1The Dana-Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts 02115, USA.

Genes & Development
|May 30, 1998
PubMed
Summary

Homozygous E2F-5 knockout mice developed hydrocephalus due to excessive cerebrospinal fluid (CSF) production. E2F-5 regulates CSF secretion in the choroid plexus, not cell proliferation.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • The choroid plexus is responsible for cerebrospinal fluid (CSF) production.
  • The role of specific transcription factors in regulating choroid plexus function is not fully understood.

Purpose of the Study:

  • To investigate the function of the E2F-5 transcription factor in embryonic development and brain function.
  • To determine if E2F-5 plays a role in cell proliferation or secretory activity of neural tissues.

Main Methods:

  • Generation of homozygous E2F-5 knockout mice and embryos.
  • Analysis of embryonic development and newborn mouse phenotypes.
  • Histological and electron microscopy examination of the choroid plexus.
  • Assessment of cell cycle kinetics in fibroblasts.

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Main Results:

  • Homozygous E2F-5 knockout mice exhibited normal embryonic development but developed nonobstructive hydrocephalus postnatally.
  • Hydrocephalus was associated with evidence of excessive CSF production.
  • The choroid plexus in knockout mice showed abundant electron-lucent epithelial cells, indicating heightened secretory activity.
  • E2F-5 expression in normal animals was predominantly localized to the choroid plexus.
  • Cell cycle kinetics in knockout fibroblasts were not perturbed, suggesting E2F-5 is not essential for proliferation.

Conclusions:

  • E2F-5 plays a critical role in regulating the secretory function of the choroid plexus.
  • E2F-5 is not essential for cell proliferation but influences the secretory behavior of differentiated neural tissue.
  • Disruption of E2F-5 function leads to excessive CSF production and hydrocephalus.