Sarah Smolik

Assistant Professor - Cell and Developmental Biology

The development of a unicellular oocyte into a complex, multicellular organism requires the combinatorial and sequential activities of a large number of genes that instruct a simple set of cells to elaborate different sets of functions and identities. Early in Drosophila embryogenesis cell fates are established by gradients of transcriptional activators that provide positional cues to a field of syncitial nuclei. These nuclei respond to the gradients in a dosage sensitive manner by expressing different batteries of genes. Once the cell membranes form, the cells maintain or change their specific identities in response to the signals received from cell-cell contacts and the environment. We have isolated the signal-responsive transcription factors dCREB-A, dCREB-B and the coactivator dCBP and generated mutations in these genes in an effort to understand how the various signals are integrated at the level of transcription. to elicit specific cellular responses. Two-hybrid screens with different domains of dCBP identified two interacting proteins; the transcription factor cubitus interruptus that mediates hedgehog signaling during development and a SIR2-like protein. The yeast SIR2 gene is required for the maintenance of silencing at the mating type loci and is presumed to act by inhibiting histone acetylation. The fact that dCBP has histone acetyltransferase activity suggests that this interaction may be critical for the maintenance of gene silencing during development. We are using genetic and molecular techniques to determine how these two interactions activate/silence transcription in response to various developmental signaling systems.

Akimaru, H., Y. Chen, P. Dai, D.-X. Hou, M. Nonaka, S. Smolik, S. Armstrong, R. H. Goodman, and S. Ishii 1997 Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signaling. Nature, 386: 735-738.

Chen, Y, J.-R.Cardinaux, R. Goodman and S. Smolik 1999 Mutants of Cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling Development , 126: 3607-3616.

Bantignies, F., R. H. Goodman and S. M. Smolik. 2000 The functional interaction between the coactivator dCBP and ASH1, a member of the trithorax group chromatin modifiers. Molec. and Cell. Biol. 20: 1616-1625.

To contact Dr. Smolik directly: smoliks@ohsu.edu