BINARY SIBLING NEURONAL CELL FATE DECISIONS IN THE DROSOPHILA EMBRYONIC CENTRAL-NERVOUS-SYSTEM ARE NONSTOCHASTIC AND REQUIRE INSCUTEABLE-MEDIATED ASYMMETRY OF GANGLION MOTHER CELLS

Asymmetric cell division is a widespread mechanism in developing tissu es that leads to the generation of cell diversity. In the embryonic ce ntral nervous system of Drosophila melanogaster; secondary precursor c ells-ganglion mother cells (GMCs)-divide and produce postmitotic neuro ns that take on different cell fates. In this study, we show that bina ry fate decision of two pairs of sibling neurons is accomplished throu gh the interplay of Notch (N) signaling and the intrinsic fate determi nant Numb. We show that GMCs have apical-basal polarity and Numb local ization and the orientation of division are coordinated to segregate N umb to only one sibling cell. The correct positioning of Numb and the proper orientation of division require Inscuteable (Insc). Loss of ins e results in the generation of equivalent sibling cells. Our results p rovide evidence that sibling neuron fate decision is nonstochastic and normally depends on the presence of Numb in one of the two siblings. Moreover, our data suggest that the fate of some sibling neurons may b e regulated by signals that do not require lateral interaction between the sibling cells.