Biochemistry of cell fusion; membrane sculpting; fertilization; organogenesis; neuronal arborization; C. elegans
Mechanism of cell fusion
We identified EFF-1 and AFF-1, two novel type I membrane proteins essential for developmental cell fusion in C. elegans. EFF-1 and AFF-1 are members of the first family (FF) of developmental cell fusion proteins (fusogens). EFF-1 and AFF-1 from nematodes and other species can fuse heterologous insect and mammalian cells. EFF-1 and AFF-1 are required in both fusing cells and the process is via hemifusion. We will purify and determine the three-dimensional structure of EFF-1 and AFF-1 proteins, we will test their fusogenic activities in cells, pseudotyped viruses and in reconstituted liposomes. Our ultimate goal is to understand the molecular and physicochemical mechanisms of cell membrane fusion. We will also search for additional members of the FF family and similar missing fusogens in other eukaryotes.
Regulation of cell fusion
We have accomplished a complete description of the cellular events leading to the formation of an organ. Using genetic analyses we identify genes that function in different cell fusion events in C. elegans and in other organisms and how this process is controlled in development.
Cell fusion and organ formation
Homotypic cell fusion may control the size of syncytia by limiting fusion with neighboring cells. We focus on fertilization, the development of vulva, epidermis, muscles and pharynx.
Evolution of organogenesis
We study cellular events during morphogenesis of the vulva across species. We found that changes in the direction of cell divisions can result in differences in size and shape of the vulva. We found that evolution of most vulval characters are biased and proposed that evolution of the vulva in nematodes is governed by selection and/or selection-independent constraints and not by stochastic processes.
Pruning of neuronal trees
We discovered that EFF-1 is also required to sculpt complex neuronal trees required for sensing strong mechanical stimuli. We found that EFF-1 trims abnormal or excessive neuronal branches as a novel quality control mechanism. EFF-1 works in specific neurons by fusing excess and abnormal neuronal branches. In addition, EFF-1 retracts branches. We have identified other genes that participate in the generation and maintenance of complex dendritic trees and we hope that our discoveries in C. elegans may help to understand and repair degenerative diseases of the nervous system and accidental breaking of neurons.
Aguilar, P.S., Baylies, M.K., Fleissner, A., Helming, L., Inoue, N., Podbilewicz, B., Wang, H., and Wong, M. (2013). Genetic basis of cell-cell fusion mechanisms. Trends Genet
Avinoam, O., Fridman, K., Valansi, C., Abutbul, I., Zeev-Ben-Mordehai, T., Maurer, U.E., Sapir, A., Danino, D., Gruenewald, K., White, J.M., and Podbilewicz, B. (2011). Conserved Eukaryotic Fusogens Can Fuse Viral Envelopes to Cells. Science 332, 589-592.