Cell division genes promote asymmetric interaction between Numb and Notch in the Drosophila CNS

Cell intrinsic and cell extrinsic factors mediate asymmetric cell divisions during neurogenesis in the Drosophila embryo, In the NB4-2-->GMC-1-->RP2/s ib lineage, one of the well-studied neuronal lineages in the ventral nerve cord, the Notch (N) signaling interacts with the asymmetrically localized N umb (Nb) to specify sibling neuronal fates to daughter cells of GMC-1, In t his current study, we have investigated asymmetric cell fate specifications by N and Nb in the context of cell cycle, We have used loss-of-function mu tations in N and nb, cell division mutants cyclinA (cycA), regulator of cyc lin Al (rca1) and string/cdc25 phosphatase (stg), and the microtubule desta bilizing agent, nocodazole, to investigate this issue, We report that the l oss of cycA, real or stg leads to a block in the division of GMC-1, however , this GMC-1 exclusively adopts an RP2 identity, While the loss of N leads to the specification of RP2 fates to both progeny of GMC-1 and loss of nb r esults in the specification of sib fates to these daughter cells, the GMC-1 in the double mutant between nb and cycA assumes a sib fate, These epistas is results indicate that both N and nb function downstream of cell division genes and that progression through cell cycle is required for the asymmetr ic localization of Nh, In the absence of entry to metaphase, the Nb protein prevents the N signaling from specifying sib fate to the RP2/sib precursor . These results are also consistent with our finding that the sib cell is s pecified as RP2 in N; nb double mutants. Finally, our results show that noc odazole-arrested GMC-1 in wild-type embryos randomly assumes either an RP2 fate or a sib fate. This suggests that microtubules are involved in mediati ng the antagonistic interaction between Nb and N during RP2 and sib fate sp ecification.