P granule biogenesis and organization

Germ granule proteins are found among a wide variety of species. In C. elegans, these granules are known as P granules. They are initially seen in the cytoplasm of oocytes and early embryos. In early embryogenesis they are asymmetrically segregated into blastomeres that eventually give rise to the germ line. In adults, P granules are peri-nuclear and cluster with nuclear pore complexes. They are associated with RNA metabolism and appear to play a role in nascent mRNA release from the nucleus.

Asymmetric cell division

In C. elegans the three principal axes of the body (Anterio/Posterior, Dorsal/Ventral, and Left/Right) are established by a series of asymmetric cell division. It's through these types of division that cell determinants are unequally segregated into daughter cells resulting in the specification of cell fates. The first cell division in C. elegans, in the one-cell embryo, results in the establishment of the A/P axis.

EGF signaling pathway

The Epidermal Growth Factor (EGF) signaling pathway was initially identified by Nobel Prize winner Stanley Cohen who found EGF to be involved in numerous cellular signaling events in mouse development. The single C. elegans EGF ligand, lin-3 and its receptor, lin-28 were initially found in screens for vulval development mutants. Further analysis of similar mutants, led to the identification of the C. elegans core EGFR signaling pathway components, SEM-5/GRB2, SOS-1, LET-60/RAS, LIN-45/RAF, MEK-2/MEK, and MPK-1. Positive regulators of this pathway were subsequently found in suppressor screens, and include KSR-1, SUR-8/SOC-2, and SUR-6. Negative modulators were found in further forward and reverse genetic screens and include UNC-101, SLI-1, GAP-1, SUR-5 and ARK-1 (in conjunction with GRB-2). LIN-3/EGF acts as a signal from the single anchor cell to induce neighboring undifferentiated epithelial cells to adopt the vulval fate during larval development. Impairing this signaling event results in a failure of vulval fate specification, and eventually a vulvaless animal that cannot lay eggs (the "bag of worms" phenotype). As in the mouse, EGF signaling was found to be involved in a number of other processes, although perhaps most importantly it is required for larval survival; homozygous let-23 null worms die at the L1 stage. Further, EGF signaling has been shown to function in coordinating vulva to uterus communication during development, promoting male spicule development, inducing P12.p cell fate in the epithelia, at the same time acting as a physiological signal, promoting ovulatory contractions of the gonad sheath cells, inducing a reversible nervous system quiescence during each larval molt, and regulating protein and calcium homeostasis in the adult worm.