PUBLICATION

Pax2/8 act redundantly to specify glycinergic and GABAergic fates of multiple spinal interneurons

Authors
Batista, M.F., and Lewis, K.E.
ID
ZDB-PUB-080902-32
Date
2008
Source
Developmental Biology   323(1): 88-97 (Journal)
Registered Authors
Batista, Manuel, Lewis, Katharine E.
Keywords
Pax2, Pax8, GABA, glycine, interneuron, spinal cord, zebrafish, Pax2a, Pax2b, neurotransmitter
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Glycine/genetics
  • Glycine/metabolism
  • Glycine/physiology*
  • Green Fluorescent Proteins/metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Interneurons/metabolism
  • Interneurons/physiology*
  • PAX2 Transcription Factor/genetics
  • PAX2 Transcription Factor/metabolism*
  • Protein Isoforms
  • Spinal Cord/metabolism
  • Spinal Cord/physiology*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • gamma-Aminobutyric Acid/genetics
  • gamma-Aminobutyric Acid/metabolism
  • gamma-Aminobutyric Acid/physiology*
PubMed
18761336 Full text @ Dev. Biol.
Abstract
The spinal cord contains several distinct classes of neurons but it is still unclear how many of the functional characteristics of these cells are specified. One of the most crucial functional characteristics of a neuron is its neurotransmitter fate. In this paper, we show that in zebrafish most glycinergic and many GABAergic spinal interneurons express Pax2a, Pax2b and Pax8 and that these transcription factors are redundantly required for the neurotransmitter fates of many of these cells. We also demonstrate that the function of these Pax2/8 transcription factors is very specific: in embryos in which Pax2a, Pax2b and Pax8 are simultaneously knocked-down, many neurons lose their glycinergic and/or GABAergic characteristics, but they do not become glutamatergic or cholinergic and their soma morphologies and axon trajectories are unchanged. In mouse, Pax2 is required for correct specification of GABAergic interneurons in the dorsal horn, but it is not required for the neurotransmitter fates of other Pax2-expressing spinal neurons. Our results suggest that this is probably due to redundancy with Pax8 and that the function of Pax2/8 in specifying GABAergic and glycinergic neuronal fates is much broader than was previously appreciated and is highly conserved between different vertebrates.
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