Neuroblast-specific open chromatin allows the temporal transcription factor, Hunchback, to bind neuroblast-specific loci

Elife. 2019 Jan 29;8:e44036. doi: 10.7554/eLife.44036.

Abstract

Spatial and temporal cues are required to specify neuronal diversity, but how these cues are integrated in neural progenitors remains unknown. Drosophila progenitors (neuroblasts) are a good model: they are individually identifiable with relevant spatial and temporal transcription factors known. Here we test whether spatial/temporal factors act independently or sequentially in neuroblasts. We used Targeted DamID to identify genomic binding sites of the Hunchback temporal factor in two neuroblasts (NB5-6 and NB7-4) that make different progeny. Hunchback targets were different in each neuroblast, ruling out the independent specification model. Moreover, each neuroblast had distinct open chromatin domains, which correlated with differential Hb-bound loci in each neuroblast. Importantly, the Gsb/Pax3 spatial factor, expressed in NB5-6 but not NB7-4, had genomic binding sites correlated with open chromatin in NB5-6, but not NB7-4. Our data support a model in which early-acting spatial factors like Gsb establish neuroblast-specific open chromatin domains, leading to neuroblast-specific temporal factor binding and the production of different neurons in each neuroblast lineage.

Keywords: D. melanogaster; DamID; chromatin; developmental biology; neuroblast; neuroscience; spatial patterning; stem cell; temporal identity.

Publication types

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

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / growth & development
  • Brain / metabolism
  • Cell Differentiation
  • Cell Lineage / genetics
  • Cell Proliferation
  • Chromatin / chemistry*
  • Chromatin / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Models, Biological
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • PAX3 Transcription Factor / genetics*
  • PAX3 Transcription Factor / metabolism
  • Protein Binding
  • Signal Transduction
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • PAX3 Transcription Factor
  • Trans-Activators
  • Transcription Factors
  • gsb protein, Drosophila
  • hb protein, Drosophila