title: The transcription factor Cux2 marks development of an A-delta sublineage of TrkA sensory neurons.
abstract: The developmental process and unique molecular identity between the many different types of dorsal root ganglion (DRG) sensory neurons generated during embryogenesis provide the cellular basis for the distinct perceptual modalities of somatosensation. The mechanisms leading to the generation of different types of nociceptive sensory neurons remain only partly understood. Here, we show that the transcription factor Cux2 is a novel marker of sensory neuron subpopulations of three main sublineages as defined by the expression of neurotrophic factor receptors TrkA, TrkB and TrkC. In particular, it is expressed in a subpopulation of early TrkA(+) neurons that arise during the early, Ngn1-independent initiated neurogenesis in the DRG. Postnatally, Cux2 marks a specific subtype of A-delta nociceptors as seen by expression of TrkA and NF200 but absence of TrpV1. Analysis of Cux2 mutant mice shows that Cux2 is not required for specification of Trk(+) neuronal subpopulations. However, Cux2 mutant mice are hypersensitive to mechanical, but not to heat or cold stimuli, consistent with a requirement in the process of specification of the mechanoreceptive neuron circuit. Hence, our results show that Cux2 is expressed and may participate in development of a specific subtype of myelinated TrkA(+) nociceptors.
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bachy
authors.forename: Marina C M
authors.initials: MC
authors.lastname: Franck
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Hind
authors.initials: H
authors.lastname: Abdo
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pattyn
authors.forename: Patrik
authors.initials: P
authors.lastname: Ernfors
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009619:Nociceptors / Q000145:classification / Q000166:cytology / Q000502:physiology; D011247:Pregnancy; D020917:Receptor, trkA / Q000502:physiology*; D020813:Receptor, trkB / Q000502:physiology; D020812:Receptor, trkC / Q000502:physiology; D011984:Sensory Receptor Cells / Q000145:classification / Q000166:cytology* / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; C101672:Cux2 protein, mouse; C102938:Neurog2 protein, mouse; C486336:Neurog1 protein, mouse