Touch receptor end-organ innervation and function require sensory neuron expression of the transcription factor Meis2.

Abstract

Touch sensation is primarily encoded by mechanoreceptors, called low-threshold mechanoreceptors (LTMRs), with their cell bodies in the dorsal root ganglia. Because of their great diversity in terms of molecular signature, terminal endings morphology, and electrophysiological properties, mirroring the complexity of tactile experience, LTMRs are a model of choice to study the molecular cues differentially controlling neuronal diversification. While the transcriptional codes that define different LTMR subtypes have been extensively studied, the molecular players that participate in their late maturation and in particular in the striking diversity of their end-organ morphological specialization are largely unknown. Here we identified the TALE homeodomain transcription factor Meis2 as a key regulator of LTMRs target-field innervation in mice. <i>Meis2</i> is specifically expressed in cutaneous LTMRs, and its expression depends on target-derived signals. While LTMRs lacking <i>Meis2</i> survived and are normally specified, their end-organ innervations, electrophysiological properties, and transcriptome are differentially and markedly affected, resulting in impaired sensory-evoked behavioral responses. These data establish <i>Meis2</i> as a major transcriptional regulator controlling the orderly formation of sensory neurons innervating peripheral end organs required for light touch.