Biology subjects

Lechasseur, X.

Publications and source records attributed to Lechasseur, X..

2 recordsLinked to original sources

bioRxiv2025

Non-autonomous PMK-1/p38 MAPK signaling ensures homeostatic downregulation of germline stem cell proliferation in C. elegans

Stem cell underproliferation leads to tissue loss while over proliferation favors hyperplasia and tumorigenesis. Stem and progenitor proliferation rates are therefore usually coupled to the needs for their differentiated cellular progenies in the tissue(s) they serve. We used the C. elegans hermaphrodite reproductive system to understand how germline stem cell (GSC) proliferation is linked to sperm availability and oocyte usage. We developed a forward genetic screening method to identify genes required for the homeostatic downregulation of GSC proliferation when oocytes are not used, where germline homeostasis defective (ghd) mutants grow benign differentiated germline tumors. We provide evidence that the TIR-1/SARM1 metabolic sensor works together with the NIPI-3/TRIB1 pseudokinase to activate a canonical PMK-1/p38 MAPK signaling cascade in the somatic gonad, shut down the extracellular regulated kinase MPK-1/ERK, and couple GSC proliferation to oocyte needs. Similar multi-tissue signaling modules could underlie homeostatic stem cell regulation and prevent benign tumorigenesis in humans.

cell biology↗

bioRxiv2020

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

Extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) is a major positive regulator of cell proliferation that is often upregulated in cancer. Yet few studies have addressed ERK/MAPK regulation of proliferation within a complete organism. The C. elegans ERK/MAPK ortholog MPK-1 is best known for its control of somatic organogenesis and germline differentiation, but it also stimulates germline stem cell proliferation. Here we identify tissue-specific MPK-1 isoforms and characterize their distinct roles in germline function. The germline-specific MPK-1B isoform promotes germline differentiation, but has no apparent role in germline stem cell proliferation. By contrast, the soma-specific MPK-1A isoform promotes germline proliferation non-autonomously. Indeed, MPK-1A functions in the intestine or somatic gonad to promote germline proliferation, independently of its other known roles. We propose that a non-autonomous role of ERK/MAPK in stem cell proliferation may be conserved across species and other tissue types, with major clinical implications for cancer and other diseases.

developmental biology↗