Neuronal Cell Fate Specification by the Convergence of Different Spatiotemporal Cues on a Common Terminal Selector Cascade

PLoS Biol. 2016 May 5;14(5):e1002450. doi: 10.1371/journal.pbio.1002450. eCollection 2016 May.

Abstract

Specification of the myriad of unique neuronal subtypes found in the nervous system depends upon spatiotemporal cues and terminal selector gene cascades, often acting in sequential combinatorial codes to determine final cell fate. However, a specific neuronal cell subtype can often be generated in different parts of the nervous system and at different stages, indicating that different spatiotemporal cues can converge on the same terminal selectors to thereby generate a similar cell fate. However, the regulatory mechanisms underlying such convergence are poorly understood. The Nplp1 neuropeptide neurons in the Drosophila ventral nerve cord can be subdivided into the thoracic-ventral Tv1 neurons and the dorsal-medial dAp neurons. The activation of Nplp1 in Tv1 and dAp neurons depends upon the same terminal selector cascade: col>ap/eya>dimm>Nplp1. However, Tv1 and dAp neurons are generated by different neural progenitors (neuroblasts) with different spatiotemporal appearance. Here, we find that the same terminal selector cascade is triggered by Kr/pdm>grn in dAp neurons, but by Antp/hth/exd/lbe/cas in Tv1 neurons. Hence, two different spatiotemporal combinations can funnel into a common downstream terminal selector cascade to determine a highly related cell fate.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism
  • Neurons / cytology*
  • Neurons / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • POU Domain Factors / genetics
  • POU Domain Factors / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Drosophila Proteins
  • GATA Transcription Factors
  • Homeodomain Proteins
  • Kr protein, Drosophila
  • Kruppel-Like Transcription Factors
  • LIM-Homeodomain Proteins
  • Lbe protein, Drosophila
  • Neuropeptides
  • Nplp1 protein, Drosophila
  • POU Domain Factors
  • Transcription Factors
  • ap protein, Drosophila
  • grn protein, Drosophila
  • kn protein, Drosophila
  • nub protein, Drosophila

Grants and funding

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was funded by Swedish Research Council (VR-NT; 621-2010-5214; www.vr.se) to ST, Wallenberg Foundation (KAW2012.0101; www.wallenberg.com/kaw/) to ST, Swedish Cancer Foundation (120531; www.cancerfonden.se) to ST, Spanish Ministerio de Economía y Competitividad (BFU2013-43858-P; http://www.idi.mineco.gob.es/portal/site/MICINN/menuitem.26172fcf4eb029fa6ec7da6901432ea0/?vgnextoid=264ecb2b1890f310VgnVCM1000001d04140aRCRD) to JBS.