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

Lei Lei, Friedrich Laub, Mark Lush, Mario Romero, Jing Zhou, Bryan Luikart, Laura Klesse, Francesco Ramirez, Luis F. Parada

Research output: Contribution to journalArticle

53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1354-1364
Number of pages11
JournalGenes and Development
Volume19
Issue number11
DOIs
StatePublished - Jun 1 2005

Keywords

  • Klf7
  • Neurotrophin
  • Nociception
  • Sensory neuron
  • Transcriptional regulation
  • TrkA

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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