title: Brn3a and Klf7 cooperate to control TrkA expression in sensory neurons.
abstract: The zinc finger protein Klf7 and POU homeodomain protein Brn3a are each required for efficient transcription of TrkA in primary sensory neurons. In this study, we examined whether these transcription factors act in concert to regulate TrkA expression. In vitro, Brn3a and Klf7 can synergistically activate the TrkA enhancer. In vivo, precursor cells that are destined to become TrkA(+) neurons are born. However, both Brn3a and Klf7 are dispensable for the initiation of TrkA expression. At E12.5, while TrkA expression is unaffected in Brn3a-/- trigeminal ganglia and only slightly decreased in Klf7-/- trigeminal ganglia, it is severely reduced in the double mutant Brn3a-/-;Klf7-/- trigeminal ganglia. At birth, all Trk(+) neurons are lost in Brn3a-/-;Klf7-/- trigeminal ganglia. We further demonstrate that the TrkA enhancer is inactive in Brn3a-/-;Klf7-/- trigeminal ganglia. Thus, cooperation between these two transcription factors is required for endogenous TrkA gene expression and the survival of nociceptive sensory neurons.
authors.affiliation: Center for Developmental Biology and Kent Waldrep Center for Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Lu
authors.initials: L
authors.lastname: Lin
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000378:metabolism* / Q000502:physiology; D010146:Pain / Q000378:metabolism; D020917:Receptor, trkA / Q000096:biosynthesis* / Q000235:genetics*; D050819:Transcription Factor Brn-3A / Q000502:physiology*
chemical_list: C426008:Klf7 protein, mouse; D051741:Kruppel-Like Transcription Factors; C494189:Pou4f1 protein, mouse; D050819:Transcription Factor Brn-3A; D020917:Receptor, trkA