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Gene Review

unc-5  -  Protein UNC-5

Caenorhabditis elegans

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High impact information on unc-5

  • In Caenorhabditis elegans, the transmembrane protein UNC-5 (ref. 14) has been implicated in these responses, as loss of unc-5 function causes migration defects and ectopic expression of unc-5 in some neurons can redirect their axons away from a netrin source [1].
  • The unc-5 gene of C. elegans encodes a unique receptor of the immunoglobulin superfamily (UNC-5), required cell-autonomously to guide growth cone and mesodermal cell migrations in a dorsal direction on the epidermis [2].
  • Genes have been identified that specify neuron type (for example cut and numb in Drosophila and mec-3 in Caenorhabditis elegans) and process guidance (for example, unc-5, unc-6 and unc-40 in C. elegans and the fas-1 gene of Drosophila) [3].
  • The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans [4].
  • In the src-1 mutant, the expression of unc-5/netrin receptor is normally regulated, and neither the precocious expression of UNC-5 nor the mutation in the unc-5 gene significantly affects the DTC migration defect [5].

Biological context of unc-5

  • We provide evidence that the transcriptional upregulation of unc-5 in the DTCs is coincident with the initiation of the second migration phase, and that premature UNC-5 expression in these cells induces precocious turning in an UNC-6-dependent manner [6].

Associations of unc-5 with chemical compounds

  • The DAF-12 steroid hormone receptor, which regulates developmental stage transitions in C. elegans, is required for initiating the first DTC turn and for coincident unc-5 upregulation [6].
  • If motor axons are mislocalized as in unc-5 mutants, GABA receptors cluster opposite ectopic axons at GABA release sites [7].

Other interactions of unc-5

  • Three known genes guide circumferential migrations of pioneer axons and mesodermal cells on the nematode body wall. unc-5 affects dorsal migrations, unc-40 primarily affects ventral migrations, and unc-6 affects migrations in both directions [4].
  • The segregation of the closely linked flanking markers, unc-17 and unc-5, revealed whether the lethal mutation was to the left or the right of m118 [8].
  • To demonstrate its utility we knocked down unc-22 in body wall muscles as well as the axon guidance gene unc-5 in the nervous system indicating that promoter-driven hairpins can overcome the neuronal resistance to RNAi [9].


  1. Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors. Leonardo, E.D., Hinck, L., Masu, M., Keino-Masu, K., Ackerman, S.L., Tessier-Lavigne, M. Nature (1997) [Pubmed]
  2. Expression of the UNC-5 guidance receptor in the touch neurons of C. elegans steers their axons dorsally. Hamelin, M., Zhou, Y., Su, M.W., Scott, I.M., Culotti, J.G. Nature (1993) [Pubmed]
  3. Mutations in the Caenorhabditis elegans unc-4 gene alter the synaptic input to ventral cord motor neurons. White, J.G., Southgate, E., Thomson, J.N. Nature (1992) [Pubmed]
  4. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Hedgecock, E.M., Culotti, J.G., Hall, D.H. Neuron (1990) [Pubmed]
  5. SRC-1, a non-receptor type of protein tyrosine kinase, controls the direction of cell and growth cone migration in C. elegans. Itoh, B., Hirose, T., Takata, N., Nishiwaki, K., Koga, M., Ohshima, Y., Okada, M. Development (2005) [Pubmed]
  6. Regulation of the UNC-5 netrin receptor initiates the first reorientation of migrating distal tip cells in Caenorhabditis elegans. Su, M., Merz, D.C., Killeen, M.T., Zhou, Y., Zheng, H., Kramer, J.M., Hedgecock, E.M., Culotti, J.G. Development (2000) [Pubmed]
  7. GABA is dispensable for the formation of junctional GABA receptor clusters in Caenorhabditis elegans. Gally, C., Bessereau, J.L. J. Neurosci. (2003) [Pubmed]
  8. Fine-structure genetics of ama-1, an essential gene encoding the amanitin-binding subunit of RNA polymerase II in Caenorhabditis elegans. Bullerjahn, A.M., Riddle, D.L. Genetics (1988) [Pubmed]
  9. pWormgatePro enables promoter-driven knockdown by hairpin RNA interference of muscle and neuronal gene products in Caenorhabditis elegans. Briese, M., Esmaeili, B., Johnson, N.M., Sattelle, D.B. Invert. Neurosci. (2006) [Pubmed]
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