HAIRLESS PROMOTES STABLE COMMITMENT TO THE SENSORY ORGAN PRECURSOR CELL FATE BY NEGATIVELY REGULATING THE ACTIVITY OF THE NOTCH SIGNALING PATHWAY

In Drosophila imaginal discs, the function of the Hairless (H) gene is required at multiple steps during the development of adult sensory or gans. Here we report the results of a series of experiments designed t o investigate the in vivo role of H in sensory organ precursor (SOP) c ell specification. We show that the proneural cluster pattern of prone ural gene expression and of transcriptional activation by proneural pr oteins is established normally in the absence of H activity. By contra st, single cells with the high levels of achaete, scabrous, and neural ized expression characteristic of SOPs almost always fail to appear in H mutant proneural clusters. These results indicate that H is require d for a relatively late step in the development of the proneural clust er, namely, the stable commitment of a single cell to the SOP cell fat e. We also show that expression of an activated form of the Notch rece ptor leads to bristle loss with the same cellular basis-failure of SOP determination-as loss of H function and that simultaneous overexpress ion of H suppresses this effect. Finally, we demonstrate by epistasis experiments that the failure of stable commitment to the SOP fate in H null mutants requires the activity of the genes of the Enhancer of sp lit complex, including groucho. Our results indicate that H promotes S OP determination by antagonizing the activity of the Notch pathway in this cell, thereby protecting it from inhibitory signaling by its neig hbors in the proneural cluster. We propose a simple threshold model in which the principal role of H in SOP specification is to translate a quantitative difference in the activity of the Notch pathway (in the S OP versus the non-SOP cells) into a stable binary cell fate decision. (C) 1995 Academic Press, Inc.