C. elegans meg‐1 and meg‐2 differentially interact with nanos family members to either promote or inhibit germ cell proliferation and survival

Abstract

Summary: The closely related C. elegans MEG-1 and MEG-2 proteins localize to P granules during a brief period of embryogenesis when the germ lineage is being separated from the soma. Embryonic primordial germ cells still develop in the absence of MEG activity, but major defects emerge during larval stages when germ cells fail to proliferate or differentiate normally, resulting in sterility. To investigate meg-1 function, we conducted a targeted RNAi screen for enhancers and suppressors of meg-1 sterility. Here, we show that meg-1 interacts with multiple pathways that promote germ cell proliferation and survival. Surprisingly, we found that two nanos family members had opposing effects on the meg-1 phenotype. Loss of nos-3 suppressed the meg-1 phenotype, restoring fertility, while loss of nos-2 enhanced the meg-1 phenotype, abolishing proliferation and causing early and pronounced germ cell degeneration. Together, our analyses suggest that, under circumstances that favor proliferation, MEG function is not essential for germ cells to proliferate, although it is important for optimal proliferation. Additionally, MEG activity is likely more directly involved in germ cell survival than previously thought. genesis 49:380-391, 2011. V V C 2011 Wiley-Liss, Inc.

Germ Cell Specification

“…Interestingly, meg-1 interacts genetically with nos-2. nos-2(RNAi);meg-1(vr10) animals show the most severe phenotype reported for Z2 and Z3: the cells never proliferate, lose perinuclear P granules, and die by the first larval stage in an apoptosis-independent manner (Kapelle and Reinke 2011). Since MEG-1 and NOS-2 expression overlaps only in P 4 , events critical for germ cell fate specification likely occur first in this cell.…”

“…MEG-1 does not contain any recognizable RNA-binding motif, but shows complex genetic interactions with RNA-binding proteins that function during larval germline development (Leacock and Reinke 2008; Kapelle and Reinke 2011). One possibility is that RNA regulation by the MEGs and other germ plasm components initiates the network of protein–RNA regulation that drives germ cell proliferation (see Chap.…”

The diverse functions of germline P‐granules in Caenorhabditis elegans

“…MEG‐1 and MEG‐2 are partially redundant, novel proteins transiently associating with P‐granules in P2 to P4 germ cells. Similar mutant phenotypes may indicate that nos and meg genes contribute to the same regulatory process, and indeed meg‐1 and nos‐2 genetically interact; the double meg‐1 ; nos‐2 mutant has a more severe phenotype that each of the single mutants (Kapelle and Reinke, ). Z2 and Z3 PGCs in the meg‐1 ; nos‐2 embryos never proliferate, disperse perinuclear P‐granules into the cytoplasm, and die by the first larval stage.…”

“…Z2 and Z3 PGCs in the meg‐1 ; nos‐2 embryos never proliferate, disperse perinuclear P‐granules into the cytoplasm, and die by the first larval stage. Germ cell death in this class of mutants is carried out by a combined effect of apoptosis and an independent “death program” (Subramaniam and Seydoux, ; Kapelle and Reinke, ). Although the germ cells in these mutants are recognizable by the localization of maternally inherited P‐granule components, it is not clear if the zygotic program of germ cell specification is fully intact.…”

Specification of the germline by Nanos-dependent down-regulation of the somatic synMuvB transcription factor LIN-15B

“…In C. elegans, the redundant nanos homologs nos-1 and nos-2 are expressed sequentially in PGCs during the maternal-to-zygotic transition and may have overlapping yet distinct effects on mRNAs stability and translation. Genetic analyses already have suggested that nos-1 and nos-2 have both unique and shared functions (Kapelle and Reinke, 2011;Mainpal et al, 2015). It will be important to determine whether nos-1 and nos-2 are both required to keep LIN-15B levels low throughout embryogenesis, and whether they act directly on the lin-15B RNA or indirectly, by silencing other factors required for LIN-15B protein translation and/or stability.…”