Establishment and maintenance of motor neuron identity via temporal modularity in terminal selector function

Elife. 2020 Oct 1:9:e59464. doi: 10.7554/eLife.59464.

Abstract

Terminal selectors are transcription factors (TFs) that establish during development and maintain throughout life post-mitotic neuronal identity. We previously showed that UNC-3/Ebf, the terminal selector of C. elegans cholinergic motor neurons (MNs), acts indirectly to prevent alternative neuronal identities (Feng et al., 2020). Here, we globally identify the direct targets of UNC-3. Unexpectedly, we find that the suite of UNC-3 targets in MNs is modified across different life stages, revealing 'temporal modularity' in terminal selector function. In all larval and adult stages examined, UNC-3 is required for continuous expression of various protein classes (e.g. receptors, transporters) critical for MN function. However, only in late larvae and adults, UNC-3 is required to maintain expression of MN-specific TFs. Minimal disruption of UNC-3's temporal modularity via genome engineering affects locomotion. Another C. elegans terminal selector (UNC-30/Pitx) also exhibits temporal modularity, supporting the potential generality of this mechanism for the control of neuronal identity.

Keywords: C. elegans; UNC-3/Ebf; UNC-30/Pitx; developmental biology; motor neurons; neuronal identity; neuroscience; transcription factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cholinergic Neurons / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Larva / genetics
  • Larva / growth & development
  • Larva / metabolism
  • Locomotion / genetics
  • Locomotion / physiology
  • Models, Neurological*
  • Motor Neurons / physiology*
  • Nervous System / growth & development
  • Nervous System / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Time Factors
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • Transcription Factors
  • unc-3 protein, C elegans
  • unc-30 protein, C elegans

Associated data

  • GEO/GSE143165