Cytoplasmic Polyadenylation Element Binding (CPEB) proteins are translational regulators that can either activate or repress translation depending on the target mRNA and the specific biological context. There are two CPEB subfamilies and most animals have one or more genes from each. Our laboratory studies CPEB of Drosophila. Drosophila has a single CPEB gene, orb and orb2, from each subfamily. Orb expression is only detected at high levels in the germline and has critical functions in oogenesis but not spermatogenesis. By contrast, orb2 is broadly expressed in the soma; and previous studies have revealed important functions in asymmetric cell division, viability, motor function, learning, and memory (Keleman et al. Nat Neurosci 10: 1587–1593, 2007; Si K et al. Cell 140: 421–435, 2010).
We showed that orb2 is also expressed in the adult male germline and that it has essential functions in programming the progression of spermatogenesis from meiosis through differentiation. Amongst the orb2 differentiation targets are orb and two other mRNAs, which are transcribed post-meiotically and localized to the tip of the flagellar axonemes. Additionally, analysis of a partial loss of function orb2 mutant suggests that the orb2 differentiation phenotypes are independent of the earlier arrest in meiosis.
Mature Drosophila sperm are highly polarized cells and orientation within the testes is important for transferring the mature sperm into the seminal vesicles (Munro et al. Cold Spring Harb Perspect Biol 1: a003400, 2009; Chia et al. Cell Biol 180: 267–272, 2008).
We demonstrated that orienting cyst polarization with respect to the main axis of the testis depends upon atypical Protein Kinase C (aPKC), a factor implicated in polarity decisions in many different biological contexts. When apkc activity is compromised in the male germline, the direction of cyst polarization within this organ is randomized. We showed that the asymmetric accumulation of aPKC protein in the cyst depends on an mRNA localization pathway that is regulated by the Drosophila CPEB protein Orb2. Orb2 is required to properly localize and activate the translation of apkc mRNAs in polarizing spermatid cysts. We alsodemonstrated that orb2 functions not only in orienting cyst polarization with respect to the apical-basal axis of the testis, but also in the process of polarization itself. One of the orb2 targets in this process is its own mRNA. Moreover, the proper execution of this orb2 autoregulatory pathway depends upon apkc.