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Gene Review

NetA  -  Netrin-A

Drosophila melanogaster

Synonyms: CG18657, CT27014, Dmel\CG18657, NetrinA, net, ...
 
 
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Disease relevance of NetA

 

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

 

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

  1. DCC's function takes shape in the nervous system. Kolodziej, P.A. Curr. Opin. Genet. Dev. (1997) [Pubmed]
  2. frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance. Kolodziej, P.A., Timpe, L.C., Mitchell, K.J., Fried, S.R., Goodman, C.S., Jan, L.Y., Jan, Y.N. Cell (1996) [Pubmed]
  3. The Drosophila Netrin receptor Frazzled guides axons by controlling Netrin distribution. Hiramoto, M., Hiromi, Y., Giniger, E., Hotta, Y. Nature (2000) [Pubmed]
  4. ROBO directs axon crossing of segmental boundaries by suppressing responsiveness to relocalized Netrin. Hiramoto, M., Hiromi, Y. Nat. Neurosci. (2006) [Pubmed]
  5. Guidance cues at the Drosophila CNS midline: identification and characterization of two Drosophila Netrin/UNC-6 homologs. Harris, R., Sabatelli, L.M., Seeger, M.A. Neuron (1996) [Pubmed]
  6. The netrin receptor frazzled is required in the target for establishment of retinal projections in the Drosophila visual system. Gong, Q., Rangarajan, R., Seeger, M., Gaul, U. Development (1999) [Pubmed]
  7. The homeobox transcription factor even-skipped regulates netrin-receptor expression to control dorsal motor-axon projections in Drosophila. Labrador, J.P., O'keefe, D., Yoshikawa, S., McKinnon, R.D., Thomas, J.B., Bashaw, G.J. Curr. Biol. (2005) [Pubmed]
  8. NETRIN and SLIT guide salivary gland migration. Kolesnikov, T., Beckendorf, S.K. Dev. Biol. (2005) [Pubmed]
  9. Characterization of Brachyury-downstream notochord genes in the Ciona intestinalis embryo. Hotta, K., Takahashi, H., Asakura, T., Saitoh, B., Takatori, N., Satou, Y., Satoh, N. Dev. Biol. (2000) [Pubmed]
  10. The midline glia of Drosophila: a molecular genetic model for the developmental functions of glia. Jacobs, J.R. Prog. Neurobiol. (2000) [Pubmed]
 
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