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Neuronal subtype specification within a lineage by opposing temporal feed-forward loops.

Magnus Baumgardt1, Daniel Karlsson, Javier Terriente

  • 1Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-581 85, Sweden.

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|December 1, 2009
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Summary

Neural stem cells generate diverse cell types through temporal gene cascades. This study reveals how the castor gene subdivides broad temporal windows into specific cell fates using opposing feed-forward loops in Drosophila.

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Area of Science:

  • Developmental biology
  • Neuroscience
  • Genetics

Background:

  • Neural progenitors generate diverse cell types over time, but the mechanisms controlling these temporal transitions remain unclear.
  • The "temporal gene cascade" in Drosophila CNS involves transcription factors altering progenitor competence.
  • How broad temporal windows in neural stem cell lineages subdivide to generate unique cell types is not well understood.

Purpose of the Study:

  • To investigate the mechanisms subdividing broad temporal windows in neural progenitor lineages.
  • To elucidate how specific cell fates are generated within broader temporal windows in the Drosophila CNS.
  • To understand the role of the castor gene in temporal progression and cell fate diversification.

Main Methods:

  • Analysis of an identifiable neural progenitor lineage in the Drosophila central nervous system (CNS).
  • Investigating the function of the castor gene and its downstream targets.
  • Identifying and characterizing feed-forward regulatory loops controlling temporal gene expression.

Main Results:

  • A broad castor temporal window was found to be subdivided by two distinct feed-forward loops, both initiated by castor.
  • The first feed-forward loop specifies a unique cell fate.
  • The second feed-forward loop suppresses the first loop, enabling the generation of alternative cell fates.

Conclusions:

  • The temporal progression of neural progenitors is regulated by gene cascades involving "temporal" and "subtemporal" genes.
  • Opposing feed-forward loops, triggered by castor, subdivide broad temporal windows to generate cell-type diversity.
  • This regulatory mechanism may be conserved across various stem cell lineages for generating cellular diversity.