GENETIC INTERACTION OF DROSOPHILA HOMOLOG OF ABELSON (ABL) PROTOONCOGENE (D-ABL) AND LETHAL(2)GIANT LARVAE (LGL) TUMOR-SUPPRESSOR GENE DURING EMBRYONIC-DEVELOPMENT

The Drosophila homologue (D-abl) of the mammalian abelson proto-oncoge ne (c-abl) encodes a cytoplasmic protein tyrosine kinase which localiz es to axons of the develop ing embryonic central nervous system (CNS) and has been shown to be required for redundant functions during axono genesis. These redundant functions become indispensable when other com ponents of the redundant pathway, such as those encoded by disabled (d ab), fasciclin I (fas I) or failed axon connection (fax) are removed f rom abl mutants Second-site mutations can thus uncover redundant aspec ts of abl-mediated axonogenesis. We used this strategy, and present ev idence to suggest a redundant function of the cytoskeletal protein enc oded by the lethal(2)giant larvae (lgl) tumour suppressor gene during embryonic axonogenesis Simultaneous mutation in lgl and abl shifts let hality of the mutations to late embryogenesis while mutation in only o ne of these genes permits development up to late larval/pupal or phara te adult stages. The lgl(-); abl(-) embryos show defective development of the CNS, characterized by loss of axonal commissures and longitudi nal axonal tracts. Lethality of the double mutation is aggravated or s uppressed by disabled (dab) or enabled (ena) mutations, which act, res pectively, as dominant enhancers or suppressors of abl. The redundant function of lgl tumour suppressor gene during axonogenesis therefore a ppears to involve aspects of D-abl-mediated signalling.