The pipsqueak-domain proteins Distal antenna and Distal antenna-related restrict Hunchback neuroblast expression and early-born neuronal identity

Development. 2011 May;138(9):1727-35. doi: 10.1242/dev.061499. Epub 2011 Mar 23.

Abstract

A fundamental question in brain development is how precursor cells generate a diverse group of neural progeny in an ordered manner. Drosophila neuroblasts sequentially express the transcription factors Hunchback (Hb), Krüppel (Kr), Pdm1/Pdm2 (Pdm) and Castor (Cas). Hb is necessary and sufficient to specify early-born temporal identity and, thus, Hb downregulation is essential for specification of later-born progeny. Here, we show that distal antenna (dan) and distal antenna-related (danr), encoding pipsqueak motif DNA-binding domain protein family members, are detected in all neuroblasts during the Hb-to-Cas expression window. Dan and Danr are required for timely downregulation of Hb in neuroblasts and for limiting the number of early-born neurons. Dan and Danr function independently of Seven-up (Svp), an orphan nuclear receptor known to repress Hb expression in neuroblasts, because Dan, Danr and Svp do not regulate each other and dan danr svp triple mutants have increased early-born neurons compared with either dan danr or svp mutants. Interestingly, misexpression of Hb can induce Dan and Svp expression in neuroblasts, suggesting that Hb might activate a negative feedback loop to limit its own expression. We conclude that Dan/Danr and Svp act in parallel pathways to limit Hb expression and allow neuroblasts to transition from making early-born neurons to late-born neurons at the proper time.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental / genetics
  • Models, Biological
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / physiology
  • Neurons / metabolism
  • Neurons / physiology*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Receptors, Steroid / genetics
  • Receptors, Steroid / physiology
  • Time Factors
  • Tissue Distribution
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • Receptors, Steroid
  • Transcription Factors
  • dan protein, Drosophila
  • danr protein, Drosophila
  • hb protein, Drosophila
  • psq protein, Drosophila
  • svp protein, Drosophila