Karin Kiontke

ABSTRACT

The timing of developmental events is critical. I am particularly interested in the events that happen at the transition from a juvenile to an adult animal, the period referred to as puberty. In humans, it occurs between ages 12 and 16, neither earlier, nor later. There are genetic disorders that lead to puberty happening way early or much too late. What determines the onset of puberty? We cannot study this in humans very well, but model organisms, even distantly related ones, provide a great system to learn about the molecular basis of developmental events.C. elegans has been particularly informative for studying developmental timing. In my lab, we have discovered a new gene that is absolutely required for mail tail tip morphogenesis, a process that marks the transition from the juveniles to adults in the worm. This gene, lep-5, turned out to be a long non-coding RNA. The way we discovered this was fascinating: there was a point mutation in a region outside of the predicted protein with a complete loss-of-function phenotype. The predicted protein sequence was not conserved but much of the nucleotide sequence was. We could replace theC. elegans sequence of the gene with sequences of other species and rescue the phenotype. The point mutation changes the predicted secondary structure of the RNA. When we restored this structure with another mutation, the function was restored as well. We hypothesized that lep-5 functions as a molecular scaffold for two proteins in a well-characterized pathway inC. elegans. It turns out, that homologs of several genes in this pathway are present in mammals as well and mutations in these genes affect developmental timing. We predict that a lep-5 homolog is present in mammals as well, suggesting a deeply conserved molecular mechanism for timing of development across many distantly related animal groups.