A GENETIC SCREEN FOR MODIFIERS OF DEFORMED HOMEOTIC FUNCTION IDENTIFIES NOVEL GENES REQUIRED FOR HEAD DEVELOPMENT

Only a few genes have been identified that participate in the developm ental pathways which modulate homeotic (HOX) protein specificity or me diate HOX morphogenetic function, To identify more HOX pathway genes, we screened for mutations on loci on the Drosophila second chromosome that interact with the homeotic gene Deformed (Dfd). Genetic and molec ular tests on the eight genes isolated in the screen place them in thr ee general categories, Two genes appear to encode trithorax group func tions, i.e. they are general activators of Hox gene expression or func tion, Four genes encode abundant, widely expressed proteins that may b e required to mediate Dfd morphogenetic functions in certain tissues, including two genes for collagen IV protein variants. Finally two of t he genes are required for the development of a subset of embryonic Dfd -dependent structures, while leaving many other segmental structures i ntact, We cloned and characterized one of these two, which we have nam ed apontic (apt), apt is required for the elaboration of dorsal and ve ntral head structures, It encodes a 484-amino-acid protein with no sig nificant similarity to known protein sequences, The apt transcript pat tern is normal in Dfd and Scr mutants, and the Dfd and Scr transcript patterns are normal in apt mutants, We propose that npt acts in parall el to, or as a cofactor with, HOX proteins to regulate homeotic target s in the ventral gnathal region.