Disease relevance of NEO1

• Dorsal root ganglion axons are unresponsive to RGM but are converted to a responsive state by neogenin expression [1].
• Neogenin, an avian cell surface protein expressed during terminal neuronal differentiation, is closely related to the human tumor suppressor molecule deleted in colorectal cancer [2].

High impact information on NEO1

• Thus neogenin is a dependence receptor inducing cell death in the absence of RGM, whereas the presence of RGM inhibits this effect [3].
• To understand the functions of RGM-neogenin complexes in vivo, we used gene transfer technology to perturb their expression in the developing neural tube of chick embryos [3].
• Here, an expression cloning strategy identified neogenin as a binding site for RGM, with a sub-nanomolar affinity [1].
• The deduced amino acid sequence and structure of neogenin characterize it as a member of the immunoglobulin (Ig) superfamily [2].
• Based on amino acid sequence similarities, neogenin is closely related to the human tumor suppressor molecule DCC (deleted in colorectal cancer) [2].

Biological context of NEO1

• Surprisingly, neogenin over-expression or RGM down-expression in the neural tube induces apoptosis [3].
• These parallels suggest that neogenin, like DCC, is functionally involved in the transition from cell proliferation to terminal differentiation of specific cell types [2].
• We showed previously that RGMa is a cell-survival factor in the neuroepithelium of chick embryos that suppresses the proapoptotic activity of its receptor neogenin [4].
• Neogenin is also expressed in other embryonic tissues, suggesting a more general role in developmental processes such as tissue growth regulation, cell-cell recognition, and cell migration [5].

Anatomical context of NEO1

• Neogenin is also found on cells in the lower gastrointestinal tract of embryonic chickens [2].
• Since neogenin is expressed on growing neurites and downregulated at termination of neurite growth, it may also play an important role in many of the complex functional aspects of neurite extension and intercellular signaling [2].
• In vitro analysis with retinal explants showed that RGM repels temporal retinal axons and collapses their growth cones through neogenin-mediated signaling [6].
• Neogenin, a protein with nearly 50% amino acid identity to DCC, was recently identified because of its dynamic expression in the developing nervous system and gastrointestinal tract of the chicken [7].

Physical interactions of NEO1

• Thus, RGM/neogenin is a novel dependence ligand/receptor couple as well as an axon guidance molecular complex [6].

Other interactions of NEO1

• Characterization of Netrin-1, Neogenin and cUNC-5H3 expression during chick dorsal root ganglia development [8].
• Like DCC, the neogenin protein consists of four immunoglobulin-like (Ig-like) domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain [5].

Analytical, diagnostic and therapeutic context of NEO1

• As revealed by antibody staining of tissue sections and Western blots, neogenin expression correlates with the onset of neuronal differentiation [2].

References