title: Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans.
abstract: Netrins are laminin-related proteins that guide circumferential migrations on the ectoderm. To understand how netrin cues direct cell movements, we examined the expression of nematode netrin UNC-6 from embryo to adult. UNC-6 is expressed in 12 types of neuroglia and neurons, creating a hierarchy of netrin cues in the developing nervous system. Comparing gene expression pattern with in vivo phenotypes, we suggest how multiple netrin cues, each with a characteristic role, guide cells and axons during development. We also present the molecular analysis of selective loss-of-function and null alleles. The results indicate that the biological activities of netrins are mediated through distinct protein domains. Subtle mutations in domain VI can produce selective defects in both direction- and tissue-specific guidance. EGF-like module V-2 is essential for dorsal guidance activity; we infer this module is important for interactions between UNC-6 and the dorsal guidance receptor UNC-5.
authors.affiliation: Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Wadsworth
authors.forename: H
authors.initials: H
authors.lastname: Bhatt
authors.forename: E M
authors.initials: EM
authors.lastname: Hedgecock
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins; D002465:Cell Movement; D018507:Gene Expression Regulation, Developmental; D015801:Helminth Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D000075388:Netrin-1; D000075385:Netrins; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010614:Pharynx / Q000196:embryology / Q000294:innervation; D025521:Tumor Suppressor Proteins
chemical_list: D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075385:Netrins; D025521:Tumor Suppressor Proteins; C078146:UNC-6 protein, C elegans; D000075388:Netrin-1; C088894:netrin-2