The transcription factor Cux2 marks development of an A-delta sublineage of TrkA sensory neurons

• Published in: Developmental biology 2011-12, Vol.360 (1), p.77-86
• Main Authors: Bachy, Isabelle, Franck, Marina C.M., Li, Lili, Abdo, Hind, Pattyn, Alexandre, Ernfors, Patrik
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Basic Helix-Loop-Helix Transcription Factors - deficiency; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - physiology; Capsaicin receptors; Cell Lineage; Circuits; cold; Cold stimuli; Development; Differentiation; DNA Primers - genetics; Dorsal root ganglia; Embryogenesis; Female; ganglia; Ganglia, Spinal - cytology; Ganglia, Spinal - embryology; Ganglia, Spinal - physiology; Gene Expression Regulation, Developmental; Heat; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; mutants; Mutation; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurogenesis; Neurogenesis - genetics; Neurogenesis - physiology; Neurotrophic factors; Neurotrophins; Nociceptive neurons; Nociceptors; Nociceptors - classification; Nociceptors - cytology; Nociceptors - physiology; Pain perception; Pregnancy; Receptor, trkA - physiology; Receptor, trkB - physiology; Receptor, trkC - physiology; receptors; Sensation; Sensory modality; Sensory neurons; Sensory Receptor Cells - classification; Sensory Receptor Cells - cytology; Sensory Receptor Cells - physiology; Transcription factors; TrkA receptors; TrkB receptors
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2011.09.007

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. ► Cux2 is expressed in post-mitotic neurons in dorsal root ganglia. ► Cux2 is a novel marker of sensory neurons of the TrkA, TrkB and TrkC sublineages. ► Cux2 is expressed in a subpopulation of early TrkA + neurons. ► Postnatally, Cux2 marks a specific subtype of A-delta nociceptors. ► Cux2 mutant mice are hypersensitive to mechanical stimuli.