Non-autonomous regulation of germline stem cell proliferation by somatic MPK-1/MAPK activity in C. elegans

Abstract

Highlights d Germline MPK-1B is dispensable for proliferation of germline stem cells d Germline MPK-1B is essential for gametogenesis and fertility d Somatic MPK-1A is required for a high rate of GSC proliferation d Somatic MPK-1A promotes germline proliferation from the gut or somatic gonad

Quantification of tissue-specific protein translation in whole C. elegans using O-propargyl-puromycin labeling and fluorescence microscopy

“…This is possibly due to the similarity between the coding sequences of iff-1 and its somatic ortholog iff-2 , resulting in the RNAi targeting both transcripts. It is also possible that reduction of translation in the germline has cell non-autonomous effects to signal reduction of translation in other tissues ( Lan et al., 2019 ; Robinson-Thiewes et al., 2021 ). Knockdown of either iff-1 or ifg-1 resulted in similar decreases in OPP incorporation across the whole worm ( Figure 3 H), despite having different roles promoting translation initiation and translation elongation, respectively.…”

Sensory neurons safeguard from mutational inheritance by controlling the CEP-1/p53-mediated DNA damage response in primordial germ cells

“…Vice versa, the DDR in germ cells also influences the soma such as elevating somatic endurance amid unrepaired meiotic DNA damage (Ermolaeva et al, 2013; Soltanmohammadi et al, 2022). Furthermore, endocrine signals have been observed to non-cell-autonomously influence stem cell proliferation and the DDR in mammals and C. elegans (Cinat et al, 2021; Gronke et al, 2019; Robinson-Thiewes et al, 2021; Xuefeng Chen, et al, 2011; Zhang et al, 2019). Somatic signaling cues are important for germline development and determine epigenetic memories that can last through several generations.…”

Formation of benign tumors by stem cell deregulation

“…In parallel, the presence of sperm, through release of MSPs, promotes oocyte ovulation, maintaining a high oocyte demand. This presumably activates MPK-1/ERK in the animal’s gut and/or somatic gonad, which nonautonomously promotes GSC proliferation, and sustains an elevated niche output and oocyte production [ 41 ]. (B) When sperm is depleted, ovulation is suppressed and oocytes initially accumulate in the proximal gonad, thereby reducing the demand for new oocytes.…”

“…elegans hermaphrodites despite their sustained feeding and systemically activated IIS [ 34 , 35 ]. Genetic and epistasis analyses revealed that ERK/MAPK signaling promoted GSC proliferation in parallel to IIS and that the localized homeostatic regulation relied on ERK/MAPK suppression to inhibit GSC proliferation [ 35 , 41 ]. As such, nutrition through IIS and homeostatic signaling through ERK/MAPK act in concert to promote the highest levels of GSC proliferation in C .…”

“…Interestingly, ERK/MAPK promotes SC proliferation cell nonautonomously in C . elegans from a neighboring tissue [ 41 ]. PTEN and LKB1 may therefore also regulate SC proliferation cell nonautonomously through inhibiting ERK/MAPK in this tissue.…”