Disease relevance of nkd

• In both nkd and germ line clone-derived zw3 embryos the pattern elements derived from the anterior-most part of each segment, the denticle belts, are deleted [1].

High impact information on nkd

• Few, if any, clones were found in the posterior-most regions of the naked cuticle, and none were found in the posterior compartments of the thorax [2].
• In fly embryos and imaginal discs nkd transcription is induced by Wg [3].
• Signal-inducible feedback antagonists such as nkd may limit the effects of Wnt proteins in development and disease [3].
• In the Drosophila embryo, the ventral epidermis consists of the segmental alternance of two major cell types that produce either naked cuticle or cytoplasmic extrusions known as denticles [4].
• Embryos derived from germ lines that are homozygous for zw3 mutations (zw3 embryos) have phenotypes similar to embryos that are mutant for the segment-polarity gene naked (nkd) [5].

Biological context of nkd

• Our studies suggest that Nkd targets Dsh-dependent signal transduction steps in both cytoplasmic and nuclear compartments of cells receiving the Wnt signal [6].
• Later during embryogenesis, wg specifies the differentiation of naked cuticle [7].
• Identified as a dominant enhancer of Bar (B), oro is also recessive embryonic lethal, and homozygous oro embryos show variable substitution of naked cuticle with denticles [8].

Anatomical context of nkd

• Our results suggest that the gooseberry-distal protein is required for the specification of naked cuticle in the epidermis and specific neuroblasts in the central nervous system [9].
• In the ectoderm, both gene products are required for the formation of the segmental portions marked by naked cuticle [10].

Associations of nkd with chemical compounds

• Addition of the chelating agent EDTA abolished the in vitro Nkd-Dsh interaction [11].

Physical interactions of nkd

• Yeast two hybrid and in vitro experiments indicate that Nkd directly binds to the basic-PDZ region of Dsh [12].

Regulatory relationships of nkd

• The third class of mutations eliminates ci protein later in embryogenesis and blocks the formation of the ventral naked cuticle [13].

Other interactions of nkd

• An unconventional nuclear localization motif is crucial for function of the Drosophila wnt/wingless antagonist naked cuticle [6].
• Specially timed Nkd overexpression is capable of abolishing Dsh function in a distinct signaling pathway that controls planar-cell polarity [12].
• Naked cuticle targets dishevelled to antagonize Wnt signal transduction [12].
• Here, we report that overexpression of Dfz2, but not Fz, rescues the mutant phenotype of wgPE2, an allele that produces denticle diversity but no naked cuticle [14].
• Cubitus interruptus acts to specify naked cuticle in the trunk of Drosophila embryos [15].

Analytical, diagnostic and therapeutic context of nkd

• EFX corresponds to a minimal domain required for fly or vertebrate Nkd to interact with the basic/PDZ domains of fly Dsh or vertebrate Dvl proteins in the yeast two-hybrid assay [16].

References