Control of daughter cell fates during asymmetric division: interaction of Numb and Notch.
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.
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Howard Hughes Medical Institute, University of California, San Francisco 94143-0724, USA.
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D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004330:Drosophila / Q000196:embryology; D029721:Drosophila Proteins; D005314:Embryonic and Fetal Development; D005260:Female; D007605:Juvenile Hormones / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051880:Receptors, Notch; D012679:Sense Organs / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000502:physiology
D029721:Drosophila Proteins; D007605:Juvenile Hormones; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D014157:Transcription Factors; C060606:numb protein, Drosophila