NanoDam identifies Homeobrain (ARX) and Scarecrow (NKX2.1) as conserved temporal factors in the Drosophila central brain and visual system

Dev Cell. 2022 May 9;57(9):1193-1207.e7. doi: 10.1016/j.devcel.2022.04.008. Epub 2022 Apr 27.


Temporal patterning of neural progenitors is an evolutionarily conserved strategy for generating neuronal diversity. Type II neural stem cells in the Drosophila central brain produce transit-amplifying intermediate neural progenitors (INPs) that exhibit temporal patterning. However, the known temporal factors cannot account for the neuronal diversity in the adult brain. To search for missing factors, we developed NanoDam, which enables rapid genome-wide profiling of endogenously tagged proteins in vivo with a single genetic cross. Mapping the targets of known temporal transcription factors with NanoDam revealed that Homeobrain and Scarecrow (ARX and NKX2.1 orthologs) are also temporal factors. We show that Homeobrain and Scarecrow define middle-aged and late INP temporal windows and play a role in cellular longevity. Strikingly, Homeobrain and Scarecrow have conserved functions as temporal factors in the developing visual system. NanoDam enables rapid cell-type-specific genome-wide profiling with temporal resolution and is easily adapted for use in higher organisms.

Keywords: ARX; NKX2.1; NanoDam; neural development; neural stem cells; temporal patterning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Cell Lineage
  • Drosophila / metabolism
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental
  • Neural Stem Cells* / metabolism


  • Drosophila Proteins