Mamo decodes hierarchical temporal gradients into terminal neuronal fate

Elife. 2019 Sep 23:8:e48056. doi: 10.7554/eLife.48056.

Abstract

Temporal patterning is a seminal method of expanding neuronal diversity. Here we unravel a mechanism decoding neural stem cell temporal gene expression and transforming it into discrete neuronal fates. This mechanism is characterized by hierarchical gene expression. First, Drosophila neuroblasts express opposing temporal gradients of RNA-binding proteins, Imp and Syp. These proteins promote or inhibit chinmo translation, yielding a descending neuronal gradient. Together, first and second-layer temporal factors define a temporal expression window of BTB-zinc finger nuclear protein, Mamo. The precise temporal induction of Mamo is achieved via both transcriptional and post-transcriptional regulation. Finally, Mamo is essential for the temporally defined, terminal identity of α'/β' mushroom body neurons and identity maintenance. We describe a straightforward paradigm of temporal fate specification where diverse neuronal fates are defined via integrating multiple layers of gene regulation. The neurodevelopmental roles of orthologous/related mammalian genes suggest a fundamental conservation of this mechanism in brain development.

Keywords: D. melanogaster; antennal lobe; developmental biology; mushroom body; neuronal temporal patterning; terminal selector.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / growth & development*
  • Cell Differentiation*
  • DNA-Binding Proteins / metabolism*
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Neural Stem Cells / physiology*
  • Neurons / physiology*
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • MAMO protein, Drosophila
  • Transcription Factors