Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation Academic Article uri icon

Overview

MeSH Major

  • Cell Differentiation
  • Core Binding Factor Alpha 2 Subunit
  • Core Binding Factor beta Subunit
  • Nociceptors

abstract

  • The generation of diverse neuronal subtypes involves specification of neural progenitors and, subsequently, postmitotic neuronal differentiation, a relatively poorly understood process. Here, we describe a mechanism whereby the neurotrophic factor NGF and the transcription factor Runx1 coordinate postmitotic differentiation of nonpeptidergic nociceptors, a major nociceptor subtype. We show that the integrity of a Runx1/CBFβ holocomplex is crucial for NGF-dependent nonpeptidergic nociceptor maturation. NGF signals through the ERK/MAPK pathway to promote expression of Cbfb but not Runx1 prior to maturation of nonpeptidergic nociceptors. In contrast, transcriptional initiation of Runx1 in nonpeptidergic nociceptor precursors is dependent on the homeodomain transcription factor Islet1, which is largely dispensable for Cbfb expression. Thus, an NGF/TrkA-MAPK-CBFβ pathway converges with Islet1-Runx1 signaling to promote Runx1/CBFβ holocomplex formation and nonpeptidergic nociceptor maturation. Convergence of extrinsic and intrinsic signals to control heterodimeric transcription factor complex formation provides a robust mechanism for postmitotic neuronal subtype specification.

publication date

  • September 29, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4657622

Digital Object Identifier (DOI)

  • 10.7554/eLife.10874

PubMed ID

  • 26418744

Additional Document Info

volume

  • 4

number

  • September2015