Different combinations of Notch ligands and receptors regulate V2 interneuron progenitor proliferation and V2a/V2b cell fate determination

Okigawa, S., Mizoguchi, T., Okano, M., Tanaka, H., Isoda, M., Jiang, Y.J., Suster, M., Higashijima, S.I., Kawakami, K., Itoh, M.
Developmental Biology   391(2): 196-206 (Journal)
Registered Authors
Higashijima, Shin-ichi, Itoh, Motoyuki, Jiang, Yun-Jin, Kawakami, Koichi, Mizoguchi, Takamasa, Suster, Maximiliano
Notch signaling, V2 neuron, Zebrafish
MeSH Terms
  • Animals
  • Cell Proliferation
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques/veterinary
  • Homeodomain Proteins/metabolism
  • Interneurons/cytology*
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Morpholinos/genetics
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Neural Stem Cells/cytology*
  • Neural Stem Cells/metabolism
  • Neurogenesis/genetics*
  • Receptor, Notch1/metabolism
  • Receptors, Notch/genetics*
  • Receptors, Notch/metabolism
  • Signal Transduction/genetics
  • Spinal Cord/cytology
  • Spinal Cord/embryology*
  • Ubiquitin-Protein Ligases/metabolism
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
24768892 Full text @ Dev. Biol.
The broad diversity of neurons is vital to neuronal functions. During vertebrate development, the spinal cord is a site of sensory and motor tasks coordinated by interneurons and the ongoing neurogenesis. In the spinal cord, V2-interneuron (V2-IN) progenitors (p2) develop into excitatory V2a-INs and inhibitory V2b-INs. The balance of these two types of interneurons requires precise control in the number and timing of their production. Here, using zebrafish embryos with altered Notch signaling, we show that different combinations of Notch ligands and receptors regulate two functions: the maintenance of p2 progenitor cells and the V2a/V2b cell fate decision in V2-IN development. Two ligands, DeltaA and DeltaD, and three receptors, Notch1a, Notch1b, and Notch3 redundantly contribute to p2 progenitor maintenance. On the other hand, DeltaA, DeltaC, and Notch1a mainly contribute to the V2a/V2b cell fate determination. A ubiquitin ligase Mib, which activates Notch ligands, acts in both functions through its activation of DeltaA, DeltaC, and DeltaD. Moreover, p2 progenitor maintenance and V2a/V2b fate determination are not distinct temporal processes, but occur within the same time frame during development. In conclusion, V2-IN cell progenitor proliferation and V2a/V2b cell fate determination involve signaling through different sets of Notch ligand-receptor combinations that occur concurrently during development in zebrafish.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes