HBL-1 patterns synaptic remodeling in C. elegans.
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.
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Katherine L
KL
Thompson-Peer
Jihong
J
Bai
Zhitao
Z
Hu
Joshua M
JM
Kaplan
D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D019521:Body Patterning / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000196:embryology / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D049452:Green Fluorescent Proteins; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; C117323:UNC-55 protein, C elegans; C474486:hbl-1 protein, C elegans