Faculty and Research
Robin P. Wharton, PhD
We use the fruit fly Drosophila melanogaster to understand mechanisms that underlie pattern formation in metazoans. The lab focuses on post-transcriptional gene regulation mediated by signals in the 3'-untranslated regions (UTRs) of maternal mRNAs.
Translational regulation is responsible for establishing the posterior of the embryonic body. We have shown that regulation of maternal hunchback (hb) mRNA is governed by a large complex of proteins that assemble on 32-nucleotide elements in its 3'-UTR. Assembly is nucleated by the binding of Pumilio to these elements. One focus of the lab is understanding how Pumilio recognizes specific RNA sequences, a project being pursued collaboratively with the Aggarwal lab at Mount Sinai Medical School in NY.
In addition to repressing hb, Pumilio represses the translation of maternal CyclinB mRNA in both the primordial germ cells (PGCs) and in the prospective somatic cytoplasm of the early embryo. An essential aspect of CyclinB regulation in the PGCs is recruitment of Nanos to the Pumilio/RNA complex; regulation in the somatic cytoplasm is Nanos-independent and thus, occurs via a different mechanism. Current work in the lab focuses on determining how Pumilio acts by different mechanisms on the same mRNA target in two different cytoplasmic compartments of the embryo.
Nanos protein in the embryo is derived from translation of the maternal mRNA, which itself is subject to a complex pattern of regulation. A subset of the nanos mRNA is localized to the posterior pole and translated, giving rise to the evanescent gradient of protein in the somatic cytoplasm (that regulates hb) as well as the protein that accumulates in the PGCs (to regulate CycB and other mRNAs). Most of the nanos mRNA is distributed throughout the somatic cytoplasm, where it is repressed by binding of Smaug to regulatory signals in its 3' UTR. Current experiments are designed to address the mechanisms by which Smaug represses unlocalized nanos mRNA and by which this repression is relieved at the posterior pole.
In addition to its roles in the early embryo, Nanos and Pumilio regulate many other processes in the organism. One of these is the maintenance of germline stem cell identity: in the absence of nos or pum function, germline stem cells differentiate and the gonad becomes barren, consisting only of somatic cells. Based on genetic interactions, we have identified a factor that appears to act in conjunction with Nanos in germline stem cell maintenance. This factor is a component of chromatin modification enzyme complexes. We are currently investigating the synergistic roles of Nanos and chromatin modification in stem cell behavior.