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Recombineering Hunchback identifies two conserved domains required to maintain neuroblast competence and specify early-born neuronal identity

Development. 2010 May;137(9):1421-30. doi: 10.1242/dev.048678. Epub 2010 Mar 24.

Abstract

The Hunchback/Ikaros family of zinc-finger transcription factors is essential for specifying the anterior/posterior body axis in insects, the fate of early-born pioneer neurons in Drosophila, and for retinal and immune development in mammals. Hunchback/Ikaros proteins can directly activate or repress target gene transcription during early insect development, but their mode of action during neural development is unknown. Here, we use recombineering to generate a series of Hunchback domain deletion variants and assay their function during neurogenesis in the absence of endogenous Hunchback. Previous studies have shown that Hunchback can specify early-born neuronal identity and maintain 'young' neural progenitor (neuroblast) competence. We identify two conserved domains required for Hunchback-mediated transcriptional repression, and show that transcriptional repression is necessary and sufficient to induce early-born neuronal identity and maintain neuroblast competence. We identify pdm2 as a direct target gene that must be repressed to maintain competence, but show that additional genes must also be repressed. We propose that Hunchback maintains early neuroblast competence by silencing a suite of late-expressed genes.

Publication types

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

MeSH terms

  • Animals
  • Central Nervous System / cytology
  • Central Nervous System / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Drosophila / embryology*
  • Drosophila / genetics
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Microscopy, Confocal
  • Neurogenesis / genetics*
  • Neurons / cytology*
  • Neurons / metabolism
  • POU Domain Factors / genetics
  • POU Domain Factors / metabolism
  • Protein Structure, Tertiary
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • POU Domain Factors
  • Transcription Factors
  • hb protein, Drosophila
  • pdm2 protein, Drosophila