Neuronal cell fate specification by the molecular convergence of different spatio-temporal cues on a common initiator terminal selector gene

PLoS Genet. 2017 Apr 17;13(4):e1006729. doi: 10.1371/journal.pgen.1006729. eCollection 2017 Apr.

Abstract

The extensive genetic regulatory flows underlying specification of different neuronal subtypes are not well understood at the molecular level. The Nplp1 neuropeptide neurons in the developing Drosophila nerve cord belong to two sub-classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1 neurons are specified by spatial cues; the Hox homeotic network and GATA factor grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp neurons that activate a common terminal selector feedforward cascade of col -> ap/eya -> dimm -> Nplp1. Here, we molecularly decode the specification of Nplp1 neurons, and find that the cis-regulatory organization of col functions as an integratory node for the different spatio-temporal combinatorial codes. These findings may provide a logical framework for addressing spatio-temporal control of neuronal sub-type specification in other systems.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Body Patterning / genetics
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • DNA-Binding Proteins / genetics
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Eye Proteins / genetics
  • GATA Transcription Factors / genetics*
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks
  • Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / genetics*
  • Neurons*
  • Neuropeptides / genetics*
  • POU Domain Factors / genetics
  • Signal Transduction
  • Transcription Factors / genetics*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eye Proteins
  • GATA Transcription Factors
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Neuropeptides
  • Nplp1 protein, Drosophila
  • POU Domain Factors
  • Transcription Factors
  • ap protein, Drosophila
  • cas protein, Drosophila
  • dimm protein, Drosophila
  • eya protein, Drosophila
  • grn protein, Drosophila
  • nub protein, Drosophila

Grants and funding

To ST: Cancerfonden, 140780 (www.cancerfonden.se); Vetenskapsrådet, 621-2013-5258 (www.vr.se); Knut och Alice Wallenbergs Stiftelse, KAW2011.0165 (http://www.wallenberg.com/kaw/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.