Julie Gates        2002-2006
Postdoctoral Fellow
Ph.D. University of Utah
Funded by an NIH NRSA Postdoctoral Fellowship and a Leukemia and Lymphoma Society Special Fellowship

Enabled and

other cytoskeletal regulators

at adherens junctions
julie's picture Intercellular adhesion and the actin cytoskeleton must be regulated to accommodate changes in cell shape and cell migrations that occur during development. If they are not regulated, morphogenesis is disrupted and normal development fails. Defects in dorsal closure and head involution are observed in embryos carrying mutations in integral components of the adherens junction, DE-cadherin and Armadillo (Arm) as well as the nonreceptor tyrosine kinase Abelson (Abl). Enabled (Ena) is a substrate of Abl and a member of the Ena/VASP family. Mammalian Ena/VASP proteins have been shown to promote cell adhesion and limit cell motility by regulating localized actin polymerization. We have found that ena genetically interacts with abl and arm in the epidermis and colocalizes with Arm at adherens junctions. This suggests that Ena may function at adherens junctions during morphogenesis to regulate adhesion by regulating actin polymerization.

We are utilizing both genetic loss of function and mislocalization techniques to examine Ena’s role during morphogenesis. These experiments suggest that Ena is required during the late stages of dorsal closure. We are currently examining the actin cytoskeleton of the leading edge cells. Since it is possible that Ena’s maternal contribution is masking additional roles, we are using similar techniques to remove or mislocalize maternal Ena and have found that Ena may be required during germ band retraction and head involution.

 
These experiments also reveal a role during oogenesis. Ena must be localized at the nurse cell cortex in order for the cytoplasmic actin bundles to form and/or be stabilized. When these actin bundles are not present, the nuclei are pushed into the ring canals during the rapid stage of cytoplasmic transport, preventing efficient transport. We are currently examining if cortical Ena is required for the formation or stabilization of the actin bundles and are also examining the consequences of generating germ line clones.

Publications

Gates, J., Mahaffey, J.P., Rogers, S.L., Emerson, M., Rogers, E.M., Sottile, S.L., Van Vactor, D., Gertler, F.B., and Peifer, M. (2007). Enabled plays key roles in Embryonic Epithelial Morphogenesis in Drosophila. Development, in press.

Gates, J., and Peifer, M. (2005). Can 1000 reviews be wrong? Actin, alpha-catenin and Adherens Junctions. Cell, in press.

Grevengoed, E.E., Fox, D.T., Gates, J., and Peifer, M. (2003). Balancing different types of actin polymerization at distinct sites: Roles for Ableson kinase and Enabled. Journal of Cell Biology 163, 1267-1280.

Gates, J., Lam, G., Ortiz, J.A., Losson, R. and Thummel, C.S. (2004). rigor mortis encodes a novel nuclear receptor interacting protein required for ecdysone signaling during Drosophila larval development. Development 131: in press

Gates, J. and Thummel, C.S. (2000). An enhancer trap screen for ecdysone-inducible genes required for Drosophila adult leg morphogenesis. Genetics 156, 1765-1776.

Keys, D.N., Lewis, D.L., Selegue, J.E., Pearson, B.J., Goodrich, L.V., Johnson, R.L., Gates, J., Scott, M.P. and Carroll, S.B. (1999). Recruitment of a hedgehog regulatory circuit in butterfly eyespot evolution. Science 283, 532-534.

Brakefield, P.M., Gates, J., Keys, D., Kesbeke, F., Wijngaarden, P.J., Monteiro, A., French, V. and Carroll, S.B. (1996). Development, plasticity and evolution of butterfly eyespot patterns. Nature 384, 236-242.


Warren, R.W., Nagy, L., Selegue, J., Gates, J. and Carroll, S.B. (1994). Evolution of homeotic gene regulation and function in flies and butterflies. Nature 372, 458-461.

Carroll, S.B., Gates, J., Keys, D.N., Paddock, S.W., Panganiban, G.E.F., Selegue, J.E. and Williams, J.A. (1994). Pattern formation and eyespot determination in butterfly wings. Science 265, 109-114.