title: The Kallmann syndrome gene homolog in C. elegans is involved in epidermal morphogenesis and neurite branching.
abstract: Kallmann syndrome is an inherited disorder defined by the association of anosmia and hypogonadism, owing to impaired targeting and migration of olfactory axons and gonadotropin-releasing hormone secreting neurons. The gene responsible for the X-linked form of Kallmann syndrome, KAL-1, encodes a secreted protein of still elusive function. It has been proposed that KAL-1 might be involved in some aspects of olfactory axon guidance. However, the unavailability of a mouse model, and the difficulties in studying cellular and axonal migration in vertebrates have hampered an understanding of its function. We have identified the C. elegans homolog, kal-1, and document its function in vivo. We show that kal-1 is part of a mechanism by which neurons influence migration and adhesion of epidermal cells undergoing morphogenesis during ventral enclosure and male tail formation. We also show that kal-1 affects neurite outgrowth in vivo by modulating branching. Finally, we find that human KAL-1 cDNA can compensate for the loss of worm kal-1 and that overexpression of worm or human KAL-1 cDNAs in the nematode results in the same phenotypes. These data indicate functional conservation between the human and nematode proteins and establish C. elegans as a powerful animal in which to investigate KAL function in vivo. Our findings add a new player to the set of molecules, which appear to underlie both morphogenesis and axonal/neuronal navigation in vertebrates and invertebrates.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino III, 80131 Naples, Italy. rugarli@tigem.it
authors.forename: Elena I
authors.initials: EI
authors.lastname: Rugarli
authors.forename: Elia
authors.initials: E
authors.lastname: Di Schiavi
authors.forename: Massimo A
authors.initials: MA
authors.lastname: Hilliard
authors.forename: Salvatore
authors.initials: S
authors.lastname: Arbucci
authors.forename: Cristina
authors.initials: C
authors.lastname: Ghezzi
authors.forename: Anna
authors.initials: A
authors.lastname: Facciolli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Coppola
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabio
authors.forename: Paolo
authors.initials: P
authors.lastname: Bazzicalupo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics*; D017124:Conserved Sequence; D004817:Epidermis / Q000254:growth & development*; D016326:Extracellular Matrix Proteins; D017238:Genes, Helminth; D006801:Humans; D017436:Kallmann Syndrome / Q000209:etiology; D008297:Male; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000648:ultrastructure*; D017386:Sequence Homology, Amino Acid; D013623:Tail / Q000254:growth & development
chemical_list: C076266:ANOS1 protein, human; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins