Combinatorial action of Grainyhead, Extradenticle and Notch in regulating Hox mediated apoptosis in Drosophila larval CNS

PLoS Genet. 2017 Oct 12;13(10):e1007043. doi: 10.1371/journal.pgen.1007043. eCollection 2017 Oct.

Abstract

Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer. In vivo mutagenesis of these motifs suggest that they are important for the maintenance of the activity of the enhancer rather than its initiation. We also find that Exd function is independent of its known partner homothorax in this apoptosis. We extend some of our findings to Deformed expressing region of sub-esophageal ganglia where pNBs undergo a similar Hox dependent apoptosis. We propose a mechanism where common players like Exd-Grh-Notch work with different Hox genes through region specific enhancers to pattern respective segments of larval central nervous system.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / genetics*
  • Central Nervous System / growth & development*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila / genetics*
  • Drosophila / growth & development
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Enhancer Elements, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Larva / genetics
  • Larva / growth & development
  • Male
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • N protein, Drosophila
  • Nuclear Proteins
  • Receptors, Notch
  • Transcription Factors
  • exd protein, Drosophila
  • grh protein, Drosophila
  • abd-A protein, Drosophila