The zinc finger transcription factor Klf7 is required for TrkA gene expression and development of nociceptive sensory neurons

  1. Lei Lei1,
  2. Friedrich Laub2,
  3. Mark Lush1,
  4. Mario Romero1,
  5. Jing Zhou1,
  6. Bryan Luikart1,
  7. Laura Klesse1,
  8. Francesco Ramirez2, and
  9. Luis F. Parada1,3
  1. 1Center for Developmental Biology and Kent Waldrep Center for Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas, 75390-9133, USA; 2Laboratory of Genetics and Organogenesis, Hospital for Special Surgery at Weill Medical College of Cornell University, New York, New York 10021, USA

Abstract

TrkA, the high affinity receptor for nerve growth factor (NGF), is essential for the development of nociceptive sensory and sympathetic neurons. The zinc finger transcription factor Klf7 interacts with an important cis element of the TrkA minimal enhancer and is coexpressed with TrkA in these neurons. We show that Klf7 binds to the endogenous TrkA minimal enhancer and can activate transcription from the TrkA minimal enhancer in a sequence-dependent manner. In Klf7-/- newborn mice, we find a significant reduction in sensory neurons due to increased apoptosis. The neuronal loss is restricted to nociceptive neurons that normally depend on TrkA for neurotrophic support, while other populations of somatosensory neurons appear normal. The reduction of TrkA expression in sensory neurons is a direct effect of Klf7 gene ablation, rather than a secondary effect of cell death. As a result, Klf7-/- mice have deficient response to noxious stimuli. Finally, removal of one TrkA allele exacerbates the loss of TrkA(+) neurons in Klf7-/- mice. Thus, Klf7 specifically regulates TrkA gene expression and is required for the development of a subset of nociceptive sensory neurons.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1227705.

  • 3 Corresponding author. E-MAIL luis.parada{at}utsouthwestern.edu; FAX (214) 648-1960.

    • Accepted April 18, 2005.
    • Received June 1, 2004.
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