Control of daughter cell fates during asymmetric division: interaction of Numb and Notch

Neuron. 1996 Jul;17(1):27-41. doi: 10.1016/s0896-6273(00)80278-0.


During development of the Drosophila peripheral nervous system, a sensory organ precursor (SOP) cell undergoes rounds of asymmetric divisions to generate four distinct cells of a sensory organ. Numb, a membrane-associated protein, is asymmetrically segregated into one daughter cell during SOP division and acts as an inherited determinant of cell fate. Here, we show that Notch, a transmembrane receptor mediated cell-cell communication, functions as a binary switch in cell fate specification during asymmetric divisions of the SOP and its daughter cells in embryogenesis. Moreover, numb negatively regulates Notch, probably through direct protein-protein interaction that requires the phosphotyrosine-binding (PTB) domain of Numb and either the RAM23 region or the very C-terminal end of Notch. Notch then positively regulates a transcription factor encoded by tramtrack (ttk). This leads to Ttk expression in the daughter cell that does not inherit Numb. Thus, the inherited determinant Numb bestows a bias in the machinery for cell-cell communication to allow the specification of distinct daughter cell fates.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Drosophila / embryology
  • Drosophila Proteins
  • Embryonic and Fetal Development
  • Female
  • Juvenile Hormones / physiology*
  • Male
  • Membrane Proteins / physiology*
  • Receptors, Notch
  • Sense Organs / cytology*
  • Stem Cells / cytology*
  • Transcription Factors / physiology


  • Drosophila Proteins
  • Juvenile Hormones
  • Membrane Proteins
  • N protein, Drosophila
  • Receptors, Notch
  • Transcription Factors
  • numb protein, Drosophila