kal-1 is the C. elegans homolog of Kal1 the gene responsible in human for X-. linked Kallmann Syndrome. Kallmann Syndrome is an inherited disorder caused. by defects of axonal outgrowth in the Olfactory System. Kal1 encodes a. secreted protein whose role in olfactory axon guidance is still elusive. C.. elegans is the first and only animal for which a mutant completely lacking. the function of the Kal gene has been produced. The gene is expressed in a. subset of C. elegans neurons. Main phenotypes presented by loss of function. and overexpression mutants indicate that
kal-1 is part of a redundant. mechanism by which neurons influence epidermal cells morphogenesis. In. addition
kal-1 modulates neurite branching in vivo (Rugarli et al., 2002).. In order to better understand the role played by
kal-1 in neuronal. development we used the loss of function mutant
gb503 and a panel of neuron. specific GFP markers. The most interesting results were obtained studying. HSN neuron development.
kal-1 mutants present a posteriorly directed spine,. coming out from the HSN cellular body and parallel to the antero-posterior. axis of the worm. In order to determine the cell from which KAL-1 has to be. secreted to control HSN spine formation, we used a modification of the RNA-. interference method, recently developed in the lab (Esposito G. et al.,. 2007). Using this approach we were able to reduce the function of
kal-1 in. selected neurons at the midbody of the animal and the results obtained. suggest that although KAL-1 is a secreted protein, its range of action is. limited in space.. Interestingly, the HSN-spine phenotype is completely suppressed by. mutations in
hst-6, an enzyme that modifies proteoglycans. This result is. quite surprising because mutations in this gene were originally identified. as suppressors of neuronal branching defects due to the overexpression of. KAL-1 (Bulow et al., 2002). The possible mechanism by which
kal-1 and
hst-6. cooperate to affect branch/spine formation and how this could help. elucidate the still elusive role played by
kal-1 in neuronal development,. will be discussed.