Bicoid mRNA is an anterior determinant for fly development that is produced in nurse cells before moving into the neighboring oocyte. In the simplest models, the mRNA was thought to use polarized microtubules to move to the anterior of the fly oocyte.
Now William Theurkauf and colleagues (University of Massachusetts Medical School, Worcester, MA) show that such a simple model will not work, because the mesh of oocyte microtubules is largely unpolarized. Instead, bicoid mRNA picks up transport factors in the nurse cells, before entering the oocyte and using those factors to mediate anterior localization, possibly on a polarized subset of microtubules. Without the factors, the mRNA can move on microtubules but its movement is undirected.
Byeong Cha in the Theurkauf lab began his experiments by injecting in vitro transcribed fluorescent bicoid mRNA into the center of oocytes. He found that the mRNA moved to whatever region of the oocyte cortex that was closest, including anterior and lateral areas. Bicoid mRNA enters oocytes through large ring canals in the anterior, so Theurkauf says “our initial bias was that it was just being trapped” as it entered.
But further experiments showed that fly oocytes do a more complete job than simple trapping. Cha found that injection of the fluorescent mRNA into nurse cells, followed by recovery of that injected mRNA and reinjection into the center of oocytes, resulted in full anterior localization. Theurkauf and Cha suggest that factors picked up by bicoid in the nurse cell allow the resultant complex to move along a subset of polarized microtubules that are hidden within the bulk of the nonpolarized microtubule array.
Based on mutant analysis, one protein that must be transferred from nurse cells is Exuperantia. Theurkauf is now searching for other such proteins. One approach, pursued in collaboration with Paul Macdonald's group (University of Texas at Austin), involves defining the cis elements that bicoid mRNA needs to pick up its factors in the nurse cell, and then using these sequences to fish out the binding proteins. ▪