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Functional expression of SCL/TAL1 interrupting locus (Stil) protects retinal dopaminergic cells from neurotoxin-induced degeneration.

Abstract
We previously isolated a dominant mutation, night blindness b (nbb), which causes a late onset of retinal dopaminergic cell degeneration in zebrafish. In this study, we cloned the zebrafish nbb locus. Sequencing results revealed that nbb is a homolog of the vertebrate SCL/TAL1 interrupting locus (Stil). The Stil gene has been shown to play important roles in the regulation of vertebrate embryonic neural development and human cancer cell proliferation. In this study, we demonstrate that functional expression of Stil is also required for neural survival. In zebrafish, decreased expression of Stil resulted in increased toxic susceptibility of retinal dopaminergic cells to 6-hydroxydopamine. Increases in Stil-mediated Shh signaling transduction (i.e. by knocking down the Shh repressor Sufu) prevented dopaminergic cell death induced by neurotoxic insult. The data suggest that the oncogene Stil also plays important roles in neural protection.
AuthorsJingling Li, Ping Li, Aprell Carr, Xiaokai Wang, April DeLaPaz, Lei Sun, Eric Lee, Erika Tomei, Lei Li
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 288 Issue 2 Pg. 886-93 (Jan 11 2013) ISSN: 1083-351X [Electronic] United States
PMID23166330 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Cell Cycle Proteins
  • DNA Primers
  • Hedgehog Proteins
  • Neurotoxins
  • Shha protein, zebrafish
  • Stil protein, zebrafish
  • Zebrafish Proteins
  • Oxidopamine
  • Dopamine
Topics
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Cycle Proteins
  • DNA Primers
  • Dopamine (metabolism)
  • Hedgehog Proteins (metabolism)
  • Humans
  • In Situ Hybridization
  • Molecular Sequence Data
  • Mutation
  • Neurons (cytology, drug effects, metabolism)
  • Neurotoxins (toxicity)
  • Oxidopamine (toxicity)
  • Retina (cytology, drug effects, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Zebrafish (embryology)
  • Zebrafish Proteins (chemistry, genetics, metabolism, physiology)

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