My lab investigates the molecular genetic control of pattern formation, neurogenesis, and metabolic control in C. elegans. Rotation projects are available in all three fields.
Our studies of pattern formation genes revealed that a key temporal morphogen, the LIN-14 protein, forms a temporal gradient, and that the graded level of this morphogen patterns the time axis of the C. elegans cell lineage. The 3' untranslated region of the lin-14 mRNA is under regulation to generate this temporal gradient, and this regulatory activity is supplied by the RNA products of the lin-4 gene which base-pair to the lin-14 mRNA. Our current research involves a dissection of how the lin-14/lin-4 RNA duplexes inhibit lin-14 translation, and how the LIN-14 protein actually specifies patterns of stage-specific cell lineage.
We also study transcription factor control of key events in C. elegans neurogenesis and neural function. We have found that particular homeodomain proteins mediate events in initial neurogenesis as well as maintenance of neural function. One of these genes, ttx-3, is expressed in a single interneuron that acts in a thermosensation and memory pathway. We are exploring the function of this transcription factor in the neural plasticity evident in C. elegans thermomemory. Another transcription factor, UNC-86, controls the activity of particular neurons that regulate egg-laying and smell behavioral circuits. We are developing new approaches to identify the genes regulated by these transcription factors to subserve their functions. We have discovered a C. elegans insulin signaling pathway in metabolic control that is homologous to mammalian insulin signaling. Our work has also demonstrated that a TGF-b signaling pathway converges with this insulin signaling pathway. We believe that this convergence is also true in mammalian insulin signaling. We are trying to show that mammalian homologues of these worm genes act in metabolic control and are variant in diabetic pedigrees. Our genetic analysis has identified many other molecules in these signaling pathways and is seeking more. Our discovery of these signaling molecules identifies new points of intervention for diabetes therapies.
Selected Publications:
Morris, J.Z., Tissenbaum, H.A. and G. Ruvkun. (1996). A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382: 536-538.
Ha, I., Wightman, B. and G. Ruvkun (1996). A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation. Genes & Development 10:3041-3050.
Sze, Ji Ying, Liu, Y. and G. Ruvkun. (1997). VP16-activation of the C. elegans neural specification transcription factor UNC-86 suppresses mutations in downstream genes and causes defects in neural migration and axon outgrowth. Development 124:1159-1168.