THE DROSOPHILA NEUROGENIC GENE BIG BRAIN, WHICH ENCODES A MEMBRANE-ASSOCIATED PROTEIN, ACTS CELL AUTONOMOUSLY AND CAN ACT SYNERGISTICALLY WITH NOTCH AND DELTA

In the developing nervous system of Drosophila, cells in each proneura l cluster choose between neural and epidermal cell fates. The neurogen ic genes mediate the cell-cell communication process whereby one cell adopts the neural cell fate and prevents other cells in the cluster fr om becoming neural, In the absence of neurogenic gene function, most, if not all of the cells become neural, big brain is a neurogenic gene that encodes a protein with sequence similarity to known channel prote ins, It is unique among the neurogenic genes in that previous genetic studies have not revealed any interaction between big bl ain and the o ther neurogenic genes, Furthermore, the neural hypertrophy in big brai n mutant embryos is less severe than that in embryos mutant for other neurogenic genes, In this paper, we show by antibody staining that bib is expressed in tissues that give rise to neural precursors and in ot her tissues that are affected by loss of neurogenic gene function, By immunoelectron microscopy, we found that bib is associated with the pl asma membrane and concentrated in apical adherens junctions as well as in small cytoplasmic vesicles, Using mosaic analysis in the adult, we demonstrate that big brain activity is required autonomously in epide rmal precursors to prevent neural development. Finally, we demonstrate that ectopically expressed big brain acts synergistically with ectopi cally ex-pressed Delta and Notch, providing the first evidence that bi g brain may function by augmenting the activity of the Delta-Notch pat hway, These results are consistent with bib acting as a channel protei n in proneural cluster cells that adopt the epidermal cell fate, and s erving a necessary function in the response of these cells to the late ral inhibition signal.