The human oncogene SCL/TAL1 interrupting locus is required for mammalian dopaminergic cell proliferation through the

Aprell L Carr1, Lei Sun2, Eric Lee3

  • 1Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, United States; Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, United States.

Cellular Signalling
|November 19, 2013
PubMed

Insights

The oncogene SCL/TAL1 interrupting locus (Stil) promotes neural progenitor cell proliferation via the Sonic hedgehog (Shh) pathway in dopaminergic cells. Stil is not essential for neural differentiation but may serve as a biomarker for these cells.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Oncology

Background:

  • The human oncogene SCL/TAL1 interrupting locus (Stil) is conserved across vertebrates and regulates cancer cell proliferation.
  • Its role in neural progenitor cells and differentiation remains largely unexplored.

Purpose of the Study:

  • To investigate the function of Stil in neural progenitor cell proliferation and differentiation.
  • To elucidate the involvement of the Sonic hedgehog (Shh) pathway in Stil-mediated effects.

Main Methods:

  • Utilized mammalian dopaminergic (DA) PC12 cells for experiments.
  • Employed RNAi-mediated knockdown and overexpression of Stil.
  • Manipulated the Shh pathway using Smoothened (Smo) antagonist cyclopamine and agonist purmorphamine.
  • Assessed cell proliferation rates and neurite outgrowth following nerve growth factor (NGF) treatment.

Main Results:

  • Stil knockdown decreased PC12 cell proliferation, while overexpression increased it.
  • Stil functions within the Shh pathway; Stil overexpression rescued proliferation defects caused by cyclopamine.
  • Stil knockdown-induced proliferation defects persisted despite Shh pathway activation.
  • Stil expression is not required for PC12 cell neural differentiation, as neurite outgrowth occurred normally after Stil knockdown.

Conclusions:

  • Stil plays a novel role in regulating neural progenitor cell proliferation through the Shh pathway.
  • Stil is not essential for neural differentiation in PC12 cells.
  • Stil is proposed as a potential biomarker for dopaminergic (DA) cells.

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