Disease relevance of NetA

• Deleted in colorectal cancer (DCC), a candidate tumor-suppressor gene, has recently been found to encode a netrin receptor required for axon guidance in vitro [1].

High impact information on NetA

• The phenotypes strongly resemble those of a deletion of the two Drosophila Netrin genes [2].
• Two classes of Netrin receptor, DCC and UNC-5 (refs 6-9), are required for axon guidance and are thought to mediate Netrin signals in growth cones through their cytoplasmic domains [3].
• Moreover, Frazzled itself is actively localized within the axon through its cytoplasmic domain, and thereby rearranges Netrin protein into a spatial pattern completely different from the pattern of Netrin gene expression [3].
• Frazzled-dependent guidance of one pioneer neuron in the central nervous system can be accounted for solely on the basis of this ability of Frazzled to control Netrin distribution, and not by Frazzled signalling [3].
• We show that, before reaching the segmental boundary, the longitudinal axons' responsiveness to Netrin presented on the commissure is suppressed by Roundabout (ROBO), through counteracting Gq signaling [4].

Biological context of NetA

• This CNS phenotype can be rescued by expression of either Netrin at the CNS midline, confirming an important role for Drosophila Netrins in commissural growth cone guidance [5].
• Both Netrin genes map close to each other on the X chromosome, and embryos deficient for this region exhibit defects in commissure formation [5].
• Our data suggest that Frazzled does not function as a Netrin receptor in attracting retinal fibers to the target; nor does it seem to act as a homotypic cell adhesion molecule [6].
• The homeobox transcription factor even-skipped regulates netrin-receptor expression to control dorsal motor-axon projections in Drosophila [7].
• Here, using genetics and single-cell mRNA-expression analysis, we show that expression and requirement of different Netrin receptor combinations correlate with distinct dorsal and ventral motor-axon projections in Drosophila [7].

Anatomical context of NetA

• NETRIN and SLIT guide salivary gland migration [8].
• NETRIN expression is also required in the visceral mesoderm, along which the glands move during their migration [8].
• The observation of the netrin gene expression in the notochord may provide the first molecular evidence that the ascidian notochord is a source of signals as in vertebrates [9].

Other interactions of NetA

• We have identified two Drosophila homologs of this protein family (Netrin-A and Netrin-B) [5].
• Genetic and molecular evidence of the interaction of attractive (Netrin) and repellent (Slit) signaling is reviewed and summarised in a model [10].

References