Cell
Volume 71, Issue 2, 16 October 1992, Pages 289-299
Journal home page for Cell

Article
UNC-5, a transmembrane protein with immunoglobulin and thrombospondin type 1 domains, guides cell and pioneer axon migrations in C. elegans

https://doi.org/10.1016/0092-8674(92)90357-IGet rights and content

Abstract

The unc-5 gene is required for guiding pioneering axons and migrating cells along the body wall in C. elegans. In mutants, dorsal migrations are disrupted, but ventral and longitudinal movements are largely unaffected. The gene was tagged for molecular cloning by transposon insertions. Based on genomic and cDNA sequencing, the gene encodes UNC-5, a transmembrane protein of 919 aa. The predicted extracellular N-terminus comprises two immunoglobulin and two thrombospondin type 1 domains. Except for an SH3-like motif, the large intracellular C-terminus is novel. Mosaic analysis shows that unc-5 acts in migrating cells and pioneering neurons. We propose that UNC-5 is a transmembrane receptor expressed on the surface of motile cells and growth cones to guide dorsal movements.

References (78)

  • M. Krause et al.

    A trans-spliced leader on actin mRNA in C. elegans

    Cell

    (1987)
  • J. Kyte et al.

    A simple method for displaying the hydropathic character of a protein

    J. Mol. Biol.

    (1982)
  • T.J. Mitchison et al.

    Cytoskeletal dynamics and nerve growth

    Neuron

    (1988)
  • K.M. Neugebauer et al.

    Vitronectin and thrombospondin promote retinal neurite outgrowth: developmental regulation and role of integrins

    Neuron

    (1991)
  • K.S. O'Shea et al.

    Thrombospondin and 140 kd fragment promote adhesion and neurite outgrowth from embryonic central and peripheral neurons and from PC12 cells

    Neuron

    (1991)
  • F.G. Rathjen

    Neural cell contact and axonal growth

    Curr. Opin. Cell Biol.

    (1991)
  • A.M. Spence et al.

    The product of fem-1, a nematode sex-determining gene, contains a motif found in cell cycle control proteins and receptors for cell-cell interactions

    Cell

    (1990)
  • R.J. Sugrue et al.

    Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel

    Virology

    (1991)
  • R.J. Sugrue et al.

    Palmitoylation of the influenza A virus protein

    Virology

    (1990)
  • J.E. Sulston et al.

    The embryonic cell lineage of the nematode Caenorhabditis elegans

    Dev. Biol.

    (1983)
  • X. Sun et al.

    Heparan sulfate-mediated binding of epithelial cell surface proteoglycan to thrombospondin

    J. Biol. Chem.

    (1989)
  • W.G. Wadsworth et al.

    Guidance of neuroblast migrations and axonal projections in Caenorhabditis elegans

    Curr. Opin. Neurobiol.

    (1992)
  • D. Wen et al.

    Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit

    Cell

    (1992)
  • D.F. Woods et al.

    The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions

    Cell

    (1991)
  • C. Yanisch-Perron et al.

    Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors

    Gene

    (1985)
  • P. Bornstein et al.

    A second thrombospondin gene in the mouse is similar in organization to thrombospondin 1 but does not respond to serum

  • D. Bray

    Cell Movements

    (1992)
  • J. Chenevert et al.

    A yeast gene (BEM1) necessary for cell polarization whose product contains two SH3 domains

    Nature

    (1992)
  • S.G. Clark et al.

    C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains

    Nature

    (1992)
  • J. Collins et al.

    Activation of a transposable element in the germ line but not the soma of Caenorhabditis elegans

    Nature

    (1987)
  • R. Conrad et al.

    Insertion of part of an intron into the 5′ untranslated region of a Caenorhabditis elegans gene converts it into a trans-spliced gene

    Mol. Cell. Biol.

    (1991)
  • J. Devereux et al.

    A comprehensive set of sequence analysis programs for the VAX

    Nucl. Acids Res.

    (1984)
  • J. Dodd et al.

    Axon guidance and the patterning of neural projections in vertebrates

    Science

    (1988)
  • D.G. Drubin et al.

    Homology of a yeast actin-binding protein to signal transduction proteins and myosin I

    Nature

    (1990)
  • D. Eide et al.

    Transposition of Tc1 in the nematode Caenorhabditis elegans

  • A. Fire

    Integrative transformation of Caenorhabditis elegans

    EMBO J.

    (1986)
  • M.A. Frohman et al.

    Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer

  • W. Gilbert

    The exon theory of genes

  • D. Goundis et al.

    Properdin, the terminal complement components, thrombospondin and the circumsporozoite protein of malarial parasites contain similar sequence motifs

    Nature

    (1988)
  • Cited by (354)

    • Temporal control of neuronal wiring

      2023, Seminars in Cell and Developmental Biology
    • Directed cell invasion and asymmetric adhesion drive tissue elongation and turning in C. elegans gonad morphogenesis

      2022, Developmental Cell
      Citation Excerpt :

      Whether CDC-42 and SRC-1 regulate adhesion proteins directly or indirectly merits further investigation. Thus, seamless turning of the gonad requires a navigation chemotactic signal, i.e., netrin signaling, as reported previously (Chan et al., 1996; Hedgecock et al., 1990; Leung-Hagesteijn et al., 1992), and a spatially regulated cell-matrix anchorage. In an analogous situation, chemotaxis and durotaxis collectively drive efficient neural crest cell migration in Xenopus (Shellard and Mayor, 2021).

    • Axon guidance: Netrins

      2020, Cellular Migration and Formation of Axons and Dendrites: Comprehensive Developmental Neuroscience
    • Genetic analysis of synaptogenesis

      2020, Synapse Development and Maturation: Comprehensive Developmental Neuroscience
    View all citing articles on Scopus
    View full text