The Kallmann syndrome gene homolog in C. elegans is involved in epidermal morphogenesis and neurite branching.
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.
Rugarli
Elena I
EI
Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino III, 80131 Naples, Italy. rugarli@tigem.it
Di Schiavi
Elia
E
Hilliard
Massimo A
MA
Arbucci
Salvatore
S
Ghezzi
Cristina
C
Facciolli
Anna
A
Coppola
Giuseppe
G
Ballabio
Andrea
A
Bazzicalupo
Paolo
P
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
C076266:ANOS1 protein, human; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins