Abstract
The mechanisms that establish and sharpen pattern across epithelia are poorly understood. In the developing nervous system, the first pattern elements appear as ‘proneural clusters’. In the morphogenetic furrow of the immature Drosophila retina proneural clusters emerge in a wave as a patterned array of 6–10-cell groups, which are recognizable by expression of Atonal, a basic helix–loop–helix transcription factor that is required to establish and pattern the first cell fate1,2,3. The establishment and subsequent patterning of Atonal expression requires activity of the signalling transmembrane receptor Notch2,4. Here we present in vivo and biochemical evidence that the secreted protein Scabrous associates with Notch, and can stabilize Notch protein at the surface. The result is a regulation of Notch activity that sharpens proneural cluster boundaries and ensures establishment of single pioneer neurons.
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Acknowledgements
We thank S. Artavanis-Tsakonas, N. Baker, K. Fischbach, T. Lieber, M. Mlodzik, M. Muskavitch and M. Young for strains and reagents; L. Saez for help with S2 cell transfections; S. Kidd for cell-surface biotinylation protocol; R. Kopan, E. Newberry, D. Towler, D. Ornitz, M. Tondravi, Y. Kasai, J. Skeath and members of the Cagan laboratory for discussions and comments on the manuscript. This work was supported by the NIH, NSF, a Research Associate Fellowship from the McDonnell Center for Cellular and Molecular Neurobiology (P.A.P.), and an NIH grant to M. Young (C.S.W.).
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Powell, P., Wesley, C., Spencer, S. et al. Scabrous complexes with Notch to mediate boundary formation. Nature 409, 626–630 (2001). https://doi.org/10.1038/35054566
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DOI: https://doi.org/10.1038/35054566
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