Runx transcription factors in neuronal development

Abstract

Runt-related (Runx) transcription factors control diverse aspects of embryonic development and are responsible for the pathogenesis of many human diseases. In recent years, the functions of this transcription factor family in the nervous system have just begun to be understood. In dorsal root ganglion neurons, Runx1 and Runx3 play pivotal roles in the development of nociceptive and proprioceptive sensory neurons, respectively. Runx appears to control the transcriptional regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As a consequence, Runx contributes to diverse aspects of the sensory system in higher vertebrates. In this review, we summarize recent progress in determining the role of Runx in neuronal development.

Figure 1

Runx proteins control the diversification of sensory neurons.(a) Proprioceptive (TrkC⁺) and mechanoreceptive (TrkB⁺) DRG neurons are derived from the common precursors (TrkB⁺, TrkC⁺). During segregation of two complementary sensory populations, Runx3 represses trkB expression in TrkC⁺ neurons. (b) During early postnatal periods, TrkA⁺ DRG neurons differentiate into two nociceptive subpopulations; TrkA⁺ peptidergic neurons, and Ret⁺ non-peptidergic neurons that repress trkA. In Ret⁺ non-peptidergic neurons, Runx1 represses trkA and neuropeptide CGRP. Runx1 also activates a number of nociceptor-specific G protein coupled receptors, ATP channels, and TRPV channels. (c) G protein coupled receptor MrgA, B and C are under dynamic transcriptional regulation in DRG neurons. A carboxy-terminal VWRPY motif of Runx proteins is critical for binding to Groucho corepressor. Runx1, which lacks VWRPY, fails to repress MrgA, B and C in DRG neurons.