Hedgehog Signaling Acts With the Temporal Cascade to Promote Neuroblast Cell Cycle Exit

PLoS Biol. 2013;11(2):e1001494. doi: 10.1371/journal.pbio.1001494. Epub 2013 Feb 26.

Abstract

In Drosophila postembryonic neuroblasts, transition in gene expression programs of a cascade of transcription factors (also known as the temporal series) acts together with the asymmetric division machinery to generate diverse neurons with distinct identities and regulate the end of neuroblast proliferation. However, the underlying mechanism of how this "temporal series" acts during development remains unclear. Here, we show that Hh signaling in the postembryonic brain is temporally regulated; excess (earlier onset of) Hh signaling causes premature neuroblast cell cycle exit and under-proliferation, whereas loss of Hh signaling causes delayed cell cycle exit and excess proliferation. Moreover, the Hh pathway functions downstream of Castor but upstream of Grainyhead, two components of the temporal series, to schedule neuroblast cell cycle exit. Interestingly, hh is likely a target of Castor. Hence, Hh signaling provides a link between the temporal series and the asymmetric division machinery in scheduling the end of neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Line
  • Chromatin Immunoprecipitation
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • In Situ Hybridization
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Drosophila Proteins
  • Hedgehog Proteins