Novel Genome-Engineered H Alleles Differentially Affect Lateral Inhibition and Cell Dichotomy Processes during Bristle Organ Development.

Hairless (H) encodes the major antagonist in the Notch signaling pathway, which governs cellular differentiation of various tissues in Drosophila . By binding to the Notch signal transducer Suppressor of Hairless (Su(H)), H assembles repressor complexes onto Notch target genes. Using genome engineering, three new H alleles, H FA , H LLAA and H WA were generated and a phenotypic series was established by several parameters, reflecting the residual H-Su(H) binding capacity. Occasionally, homozygous H WA flies develop to adulthood. They were compared with the likewise semi-viable H NN allele affecting H-Su(H) nuclear entry. The H homozygotes were short-lived, sterile and flightless, yet showed largely normal expression of several mitochondrial genes. Typical for H mutants, both H WA and H NN homozygous alleles displayed strong defects in wing venation and mechano-sensory bristle development. Strikingly, however, H WA displayed only a loss of bristles, whereas bristle organs of H NN flies showed a complete shaft-to-socket transformation. Apparently, the impact of H WA is restricted to lateral inhibition, whereas that of H NN also affects the respective cell type specification. Notably, reduction in Su(H) gene dosage only suppressed the H NN bristle phenotype, but amplified that of H WA . We interpret these differences as to the role of H regarding Su(H) stability and availability.