Tlx3 controls the development of C-low threshold mechanoreceptors.

Somatosensory information is signaled by primary sensory neurons located in dorsal root ganglia (DRG) or trigeminal ganglia. Type C-low threshold mechanoreceptors (C-LTMRs) are proposed to sense light touch. The differentiation and maturation of C-LTMRs are regulated by multiple transcript factors, including Zfp521 and Runx1. However, the molecular mechanism of C-LTMR development still remains largely unclear. RNA sequencing (RNA-seq) was performed to detect transcriptional changes in Tlx3cko DRGs compared to controls. In situ hybridization and RNAscope were used to verify RNA-seq data. RNA-seq identified 203 up- and 372 downregulated genes in DRG by loss of Tlx3 function. KEGG and Gene ontology analysis indicated that the biological properties and molecular functions were closely associated with neural signal processing and transmitting somatosensory information. In addition, the expression of marker genes of C-LTMRs was significantly decreased in Tlx3 mutants. However, Tlx3cko mice exhibited normal response to static and dynamic touch. Furthermore, Tlx3 was required to regulate the expression of Zfp521 and Runx1. Tlx3, Runx1 and Zfp521 may form a hierarchical regulation pathway to control C-LTMR development.

Meis1 Regulates Nociceptor Development and Behavioral Response to Tactile Stimuli.

Nociceptors in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are necessary for transmitting pain and itch signals. However, the molecular mechanism regulating nociceptor development remains largely unknown. This study identifies that the transcription factor Meis1 is generally expressed in two groups of sensory neurons in the developing DRG. During prenatal and neonatal stages, approximately 2/3 of Meis1+ neurons are Runx1+ nociceptors, while 1/3 of Meis1+ neurons are NF200+ myelinated neurons. At postnatal stages, Meis1 expression in nociceptors is gradually reduced. Here, we constructed a Meis1 conditional knockout mouse line to selectively delete Meis1 in Nav1.8 lineage nociceptors. Microarray analyses showed that differentially expressed genes in the Meis1 mutant DRG were enriched in pathways related to sensory perception of pain and nervous system development. In addition, Meis1 regulates the expression of some marker genes of Nppb+ neurons and C-LTMRs. Furthermore, Meis1 mutant mice exhibit behavioral deficits in response to light mechanical pain, static touch and chemical itch. Therefore, this study reveals that Meis1 is required to regulate the development of nociceptors.