HBL-1 patterns synaptic remodeling in C. elegans

Neuron. 2012 Feb 9;73(3):453-65. doi: 10.1016/j.neuron.2011.11.025.

Abstract

During development, circuits are refined by the dynamic addition and removal of synapses; however, little is known about the molecular mechanisms that dictate where and when synaptic refinement occurs. Here we describe transcriptional mechanisms that pattern remodeling of C. elegans neuromuscular junctions (NMJs). The embryonic GABAergic DD motor neurons remodel their synapses, whereas the later born VD neurons do not. This specificity is mediated by differential expression of a transcription factor (HBL-1), which is expressed in DD neurons but is repressed in VDs by UNC-55/COUP-TF. DD remodeling is delayed in hbl-1 mutants whereas precocious remodeling is observed in mutants lacking the microRNA mir-84, which inhibits hbl-1 expression. Mutations increasing and decreasing circuit activity cause corresponding changes in hbl-1 expression, and corresponding shifts in the timing of DD plasticity. Thus, convergent regulation of hbl-1 expression defines a genetic mechanism that patterns activity-dependent synaptic remodeling across cell types and across developmental time.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal
  • Body Patterning / genetics*
  • Caenorhabditis elegans / anatomy & histology
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental / genetics*
  • Green Fluorescent Proteins / genetics
  • Motor Neurons / physiology*
  • Mutation / genetics
  • Neuromuscular Junction / embryology
  • Neuromuscular Junction / genetics*
  • Receptors, Cell Surface / physiology
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • UNC-55 protein, C elegans
  • hbl-1protein, C elegans
  • Green Fluorescent Proteins
  • gamma-Aminobutyric Acid